SUN1058: A Study In Patients With Non-Small Cell Lung Cancer Testing If Erlotinib Plus SU011248 (Sunitinib) Is Better Than Erlotinib Alone
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00265317
Collaborator
(none)
162
32
2
67
5.1
0.1
Study Details
Study Description
Brief Summary
This study will test whether treatment with erlotinib plus SU011248 is better than erlotinib alone in patients with advanced/metastatic lung cancer who have received previous treatment with a platinum-based regimen
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
162 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Randomized, Double-Blind, Phase 2 Study Of Erlotinib With Or Without SU011248 In The Treatment Of Metastatic Non-Small Cell Lung Cancer
Study Start Date
:
Jun 1, 2006
Actual Primary Completion Date
:
Jan 1, 2010
Actual Study Completion Date
:
Jan 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A
|
Drug: erlotinib
erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
Drug: sunitinib
Sunitinib 37.5 mg daily by oral capsule in a continuous regimen plus erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
Other Names:
|
| Active Comparator: B
|
Drug: erlotinib
erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
Drug: placebo
Placebo daily by oral capsule in a continuous regimen plus erlotinib 150 mg daily by tablets in a continuous regimen, until progression or unacceptable toxicity
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS=time from randomization date to date of first documentation of progressive disease (PD; defined as greater than or equal to [≥]20% increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since first dose or appearance of ≥1 new lesions) or death on-study due to any cause, whichever occurred first based on third party independent imaging review laboratory assessment. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02. Used 7.02 days as it equals 365 days per year divided by 52 weeks per year.
Secondary Outcome Measures
- Percentage of Participants With Objective Response [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
Objective Response Rate (ORR)=participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST,Version 1.0) based on third party independent imaging review laboratory assessment. A CR was defined as the disappearance of all target lesions that persisted on repeat imaging study at least 4 weeks after initial documentation of response. A PR was defined as a ≥30% decrease in sum of longest dimensions of target lesions taking as a reference the baseline sum longest dimensions.
- Time to Tumor Progression (TTP) [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
TTP was defined as the time from date of randomization to first documentation of PD based on third party independent imaging review laboratory assessment. TTP was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Duration of Response (DR) [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
DR was defined as time from first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of PD or death on-study due to any cause, whichever occurred first. DR was calculated as (first date of PD or death minus first date of CR or PR that was subsequently confirmed plus 1) divided by 7.02.
- Overall Survival (OS) [From randomization until death (up to Month 17)]
OS was defined as time from date of randomization to date of death due to any cause. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.
- Percentage of Participants Surviving at 1 Year [From randomization until death (up until Month 17)]
Percentage of participants alive at 1 year after date of first administration of study medication.
- Area Under the Curve From Time Zero to 24 Hours [AUC(0-24)] of Erlotinib [Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of erlotinib
- AUC(0-24) of Sunitinib [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of sunitinib
- AUC(0-24) of SU-012662 (Metabolite of Sunitinib) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of SU-012662 (metabolite of sunitinib)
- AUC(0-24) of Total Drug (Sunitinib + SU-012662) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of total drug (sunitinib + SU-012662)
- Maximum Observed Plasma Concentration (Cmax) of Erlotinib [Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
- Cmax of Sunitinib [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Cmax of SU-012662 (Metabolite of Sunitinib) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Cmax of Total Drug (Sunitinib + SU-012662) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) for Erlotinib [Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose; predose on Days 22 and 23 (Cycle 1)]
AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for erlotinib. It is obtained from AUC from time zero (pre-dose) to last quantifiable concentration(AUC[0-t]) plus AUC from time last quantifiable concentration extrapolated infinite time (AUC[t-inf])
- AUC(0-inf) for Sunitinib [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1)]
AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for sunitinib. It is obtained from AUC(0-t) plus AUC(t-inf)
- AUC(0-inf) for SU-012662 (Metabolite of Sunitinib) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1)]
AUC(0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for SU-012662 (metabolite of sunitinib). It is obtained from AUC(0-t) plus AUC(t-inf)
- AUC(0-inf) for Total Drug (Sunitinib + SU-012662) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1)]
AUC(0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for total drug (sunitinib + SU-012662). It is obtained from AUC(0-t) plus AUC(t-inf)
- Plasma Decay Half-life (t1/2) of Erlotinib [Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Plasma Decay Half-life (t1/2) of Sunitinib [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Erlotinib Clearance at Steady State After Oral Administration (CL/F) [Day 15 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
- Sunitinib Clearance at Steady State After Oral Administration (CL/F) [Day 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Erlotinib [Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose]
- Tmax for Sunitinib [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Tmax for SU-012662 (Metabolite of Sunitinib) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Tmax for Total Drug (Sunitinib + SU-012662) [Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose]
- Dose-Corrected Observed Plasma Trough Concentrations (Ctrough) for Erlotinib on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18)]
Ctrough = plasma concentration of erlotinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.
- Dose-Corrected Ctrough for Erlotinib on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [predose Day 15 (Cycle1); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18)]
Ctrough = plasma concentration of erlotinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.
- Dose-Corrected Ctrough for Sunitinib on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18)]
Ctrough = plasma concentration of sunitinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.
- Dose-Corrected Ctrough for Sunitinib on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18)]
Ctrough = plasma concentration of sunitinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.
- Dose-Corrected Ctrough for SU-012662 (Metabolite of Sunitinib) on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18)]
Ctrough = plasma concentration of SU-012662 prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.
- Dose-Corrected Ctrough for SU-012662 (Metabolite of Sunitinib) on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) [predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18)]
Ctrough = plasma concentration of SU-012662 prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18.
- Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression by Immunohistochemistry (IHC) Using 0 Percent [%] Cutoff [Baseline]
Percentage of participants with EGFR expression by IHC using a 0% cutoff; Reported as positive, negative, or unmeasured (where positive was greater than 0% of cells demonstrating membranous staining for EGFR). Correlative analysis of EGFR expression was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.
- PFS in Subgroups That Were Defined by EGFR Expression (Using 0% Cutoff) [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS defined as time in weeks from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in the following subgroups: positive, negative, or unmeasured EGFR expression. EGFR expression was analyzed using a 0% cutoff where positive was greater than 0% of cells demonstrating membranous staining for EGFR. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Percentage of Participants With EGFR Expression by IHC (Using 10% Cutoff) [Baseline]
Percentage of participants with EGFR Expression by IHC using a 10% cutoff; Reported as positive (positive values were defined as being greater than 10% of cells demonstrating membranous staining for EGFR), negative, or unmeasured. Correlative analysis of EGFR expression was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.
- PFS in Subgroups That Were Defined by EGFR Expression (Using 10% Cutoff) [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS defined as time in weeks from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in the following subgroups: positive, negative, or unmeasured EGFR expression. EGFR expression was analyzed using a 10% cutoff where positive was greater than 10% of cells demonstrating membranous staining for EGFR. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Percentage of Participants With EGFR Gene Copy Number Increase [Baseline]
The number of copies corresponding to exon 19 of the EGFR gene was determined by real-time quantitative polymerase chain reaction (PCR). The percentage of participants with EGFR Gene Copy Number Increase (defined as greater than 4 copies) was determined using deoxyribonucleic acid (DNA) from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. Reported as yes, no or unmeasured.
- PFS in Subgroups That Were Defined by EGFR Gene Copy Number Increase [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to the date of the first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene copy number increase (reported as yes, no, or unmeasured). The number of copies corresponding to exon 19 of the EGFR gene was determined and an increase was defined as greater than 4 copies. PFS was calculated as (first event date minus randomization date plus 1)/7.02.
- Percentage of Participants With EGFR Gene Amplification [Baseline]
The percentage of participants with EGFR gene amplification (defined as greater than 15) was determined and reported as yes, no, or unmeasured. Correlative analysis of EGFR gene amplification was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.
- PFS in Subgroups That Were Defined by EGFR Gene Amplification [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene amplification (defined as greater than 15) and reported as no or unmeasured. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Percentage of Participants With EGFR Gene Mutation [Baseline]
Mutations in exons 18 through 21 of the EGFR gene were analyzed by high-performance liquid chromatography using DNA from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. The percentage of participants with EGFR mutations categorized as mutated, wild type or indeterminate was reported.
- PFS in Subgroups That Were Defined by EGFR Gene Mutation [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to date of first documentation of PD or to death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene mutation (reported as mutated, wild type, or indeterminate). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Percentage of Participants With KRAS (V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog) Gene Mutations [Baseline]
Mutations in exons 2-3 of the KRAS gene (including codons 12, 13, and 61) were analyzed by high-performance liquid chromatography using DNA from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. The percentage of participants with KRAS mutations categorized as mutated, wild type or indeterminate was reported.
- PFS in Subgroups That Were Defined by KRAS Gene Mutation [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by KRAS gene mutation (reported as mutated, wild type, or indeterminate). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Percentage of Participants With Germline Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Polymorphisms [Baseline]
Blood samples were collected at baseline for multiplex reverse transcription (RT) analysis of genes expressing proteins that are targets of sunitinib or involved in angiogenesis or tumor growth to determine expression levels. Percentage of participants with germline VEGFR2 single nucleotide polymorphisms (SNPs) was reported for the following genotype frequencies: homozygous C alleles (C/C), T alleles (T/T), G alleles (G/G), or A alleles (A/A), and the following heterozygous genotypes C/T, G/T, T/A, and G/A.
- PFS in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by VEGFR2 polymorphisms. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Overall Survival (OS) in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms [From randomization until death (up to Month 17)]
OS, defined as time from date of randomization to date of death due to any cause, in subgroups that were defined by VEGFR2 polymorphisms. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4.
- Percentage of Participants With Germline Platelet-derived Growth Factor Receptor Beta (PDGFRB) Polymorphisms [Baseline]
Blood samples were collected at baseline for multiplex RT analysis of genes expressing proteins that are targets of sunitinib or involved in angiogenesis or tumor growth to determine expression levels. Percentage of participants with germline PDGFRB SNPs was reported for the following genotype frequencies: homozygous C alleles (C/C), T alleles (T/T), G alleles (G/G), or A alleles (A/A), and the following heterozygous genotypes C/T, A/T, A/G, T/C, T/G, G/C, C/A and G/A.
- PFS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by PDGFRB polymorphisms. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- OS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
OS, defined as time from date of randomization to date of death due to any cause, in subgroups that were defined by PDGFRB polymorphisms. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4.
- Percentage of Participants by Tumor VEGFR Mutation [Baseline]
Percentage of participants with VEGFR mutations in DNA from tumor samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.
- Correlation of Polymorphisms in Stem Cell Factor Receptor (c-Kit), FMS-like Tyrosine Kinase 3 Receptor (FLT-3), and c-FMS With Blood Counts [Baseline (Day 1, Cycle 1)]
A blood sample (6 mL) was collected before on-study treatment and was used to isolate DNA. These samples were not anonymized. Correlation was investigated by the percentage of participants with anemia (based on hemoglobin count), neutropenia (based on neutrophil count) and thrombocytopenia (based on platelet count) endpoints and genetic variation as measured by c-KIT, FLT-3, and c-FMS was to be analyzed.
- Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile [Baseline]
Includes colony-stimulating factor 1 receptor (CSF-1R), PDGFRalpha, PDGFRbeta, vascular endothelial growth factor (VEGF), VEGF C (VEGF-C), VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), VEGF receptor 3 (VEGFR3), fibroblast growth factor (FGF), FLT-3, KIT (stem cell factor receptor), and RET (rearranged during transfection). Correlative analysis was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable.
- PFS in Subgroups That Were Defined by RNA Expression Profile [From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17)]
PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by RNA Gene expression (CSF-1R, PDGFRalpha, PDGFRbeta, VEGF, VEGF-C, VEGFR1, VEGFR2, VEGFR3, FGF, FLT-3, KIT, and RET). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02.
- Health Related Quality of Life (HRQoL) and Lung Cancer Related Symptoms as Assessed With European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score [Baseline (Cycle [C] 1, Day [D] 1) to Cycle 18, Day 1]
EORTC QLQ-C30: self-administered questionnaire assessing global health status/quality of life (QoL), functional domains (physical, role, cognitive, emotional, and social), symptom scales/items (fatigue, pain, nausea and vomiting, dyspnea, insomnia, loss of appetite, constipation, and diarrhea), and financial difficulties. Recall period: past week; response range: not at all (1) to very much (4); global/QoL range: very poor (1) to excellent (7). Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
- EORTC-QLQ-C30 Lung Cancer Module (LC13) Score [Baseline (Cycle 1 [Day 1]) to Cycle 18 (Day 1)]
The EORTC-QLQ-C30 LC13 is a self-administered questionnaire assessing specific lung cancer disease related symptoms (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in the chest, arm/shoulder or other parts of the body). Recall period: past week; response range: not at all (1) to very much (4). Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
- Number of Participants With Blood Pressure (BP) Greater Than 150/100 Millimeters of Mercury (mmHg) [Randomization up until Month 17]
Systolic/diastolic BP measured in triplicate (separated by approximately 2 minutes [min]) using validated electronic device (same device for all measurements), recorded to nearest mmHg. Dominant arm used (same one each time) with appropriate cuff size encircling at least 80% of arm. BP measured after 5 min rest and before invasive procedures, while seated in a chair with back supported, arms bared, supported at heart level. No smoking or caffeine use allowed during 30 min before measurement. Number of participants with systolic BP >150 mmHg/diastolic BP >100 mmHg at any timepoint postbaseline.
- Number of Participants With BP Greater Than 200/110 mmHg [Randomization up until Month 17]
Systolic/diastolic BP measured in triplicate (separated by approximately 2 minutes [min]) using validated electronic device (same device for all measurements), recorded to nearest mmHg. Dominant arm used (same one each time) with appropriate cuff size encircling at least 80% of arm. BP measured after 5 min rest and before invasive procedures, while seated in a chair with back supported, arms bared, supported at heart level. No smoking or caffeine use allowed during 30 min before measurement. Number of participants with systolic BP >150 mmHg/diastolic BP >100 mmHg at any timepoint postbaseline.
- Number of Participants on Anti-hypertensive Medications [Randomization to Day 28 of Cycle 18]
Number of participants with BP greater than 150/100 mmHg or 200/110 mmHg who were treated with anti-hypertensive medications.
- Plasma Concentration of VEGF-C at Baseline [Baseline (Cycle 1, Day 1)]
- Plasma Concentration of Soluble VEGFR-2 at Baseline [Baseline (Cycle 1, Day 1)]
- Plasma Concentration of Soluble VEGFR-3 at Baseline [Baseline (Cycle 1, Day 1)]
- Plasma Concentration of Soluble KIT (sKIT) at Baseline [Baseline (Cycle 1, Day 1)]
Other Outcome Measures
- VEGF-C Ratio to Baseline at Each Timepoint [Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)]
Plasma VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline)
- VEGFR-2 Ratio to Baseline at Each Timepoint [Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)]
Plasma VEGFR-2 concentration at each time point divided by VEGFR-2 concentration at baseline (ratio to baseline)
- VEGFR-3 Ratio to Baseline at Each Timepoint [Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)]
Plasma VEGFR-3 concentration at each time point divided by VEGFR-3 concentration at baseline (ratio to baseline)
- sKIT Ratio to Baseline at Each Timepoint [Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1)]
Plasma sKIT concentration at each time point divided by sKIT concentration at baseline (ratio to baseline)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with locally advanced/metastatic non-small cell lung cancer
-
Prior treatment with no more than 2 chemotherapy regimens including a platinum-based regimen
Exclusion Criteria:
-
Prior treatment with any receptor tyrosine kinase inhibitors, Vascular endothelial growth factor (VEGF) inhibitors or other angiogenic inhibitors
-
History of or known brain metastases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Birmingham | Alabama | United States | 35233 |
| 2 | Pfizer Investigational Site | Birmingham | Alabama | United States | 35294 |
| 3 | Pfizer Investigational Site | Mobile | Alabama | United States | 36604 |
| 4 | Pfizer Investigational Site | Antioch | California | United States | 94531 |
| 5 | Pfizer Investigational Site | Palm Springs | California | United States | 92262-4885 |
| 6 | Pfizer Investigational Site | Pleasant Hill | California | United States | 94523 |
| 7 | Pfizer Investigational Site | San Leandro | California | United States | 94578 |
| 8 | Pfizer Investigational Site | Chicago | Illinois | United States | 60612 |
| 9 | Pfizer Investigational Site | Creve Coeur | Missouri | United States | 63141 |
| 10 | Pfizer Investigational Site | St. Louis | Missouri | United States | 63110-1094 |
| 11 | Pfizer Investigational Site | St. Louis | Missouri | United States | 63110 |
| 12 | Pfizer Investigational Site | St. Peters | Missouri | United States | 63376 |
| 13 | Pfizer Investigational Site | Chapel Hill | North Carolina | United States | 27599-7600 |
| 14 | Pfizer Investigational Site | Clinton | North Carolina | United States | 28328 |
| 15 | Pfizer Investigational Site | Goldsboro | North Carolina | United States | 27534 |
| 16 | Pfizer Investigational Site | Wilson | North Carolina | United States | 27893 |
| 17 | Pfizer Investigational Site | Cleveland | Ohio | United States | 44106 |
| 18 | Pfizer Investigational Site | Houston | Texas | United States | 77030 |
| 19 | Pfizer Investigational Site | Edmonton | Alberta | Canada | T6G 1Z2 |
| 20 | Pfizer Investigational Site | Hamilton | Ontario | Canada | L8V 5C2 |
| 21 | Pfizer Investigational Site | Budapest | Hungary | 1525 | |
| 22 | Pfizer Investigational Site | Torokbalint | Hungary | 2045 | |
| 23 | Pfizer Investigational Site | Genova | Italy | 16132 | |
| 24 | Pfizer Investigational Site | Monteforte Irpino, AV | Italy | 83024 | |
| 25 | Pfizer Investigational Site | Amsterdam | Netherlands | 1066 CX | |
| 26 | Pfizer Investigational Site | Groningen | Netherlands | 9713 GZ | |
| 27 | Pfizer Investigational Site | Bydgoszcz | Poland | 85-796 | |
| 28 | Pfizer Investigational Site | Gdansk | Poland | 80-952 | |
| 29 | Pfizer Investigational Site | Cluj-Napoca | Cluj | Romania | 400015 |
| 30 | Pfizer Investigational Site | Bucuresti | Sector 2 | Romania | 022328 |
| 31 | Pfizer Investigational Site | Bucuresti | Romania | 30171 | |
| 32 | Pfizer Investigational Site | Santander | Cantabria | Spain | 39008 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00265317
Other Study ID Numbers:
- A6181058
First Posted:
Dec 14, 2005
Last Update Posted:
Feb 6, 2013
Last Verified:
Jan 1, 2013
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-in) | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules once daily (QD) for 28 days each cycle with exception of Cycle 2 (27 days) and Erlotinib 150 mg oral tablets QD for 28 days each cycle with exception of Cycle 1 (35 days). | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1, Arm A or 13 days in Cycle 1, Arm B) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1, Arm A or 26 days in Cycle 1, Arm B) | Sunitinib oral capsules, 37.5 mg QD in a continuous regimen, expressed in 4-week cycles and Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Period Title: Lead-In | ||||
| STARTED | 13 | 17 | 0 | 0 |
| COMPLETED | 1 | 0 | 0 | 0 |
| NOT COMPLETED | 12 | 17 | 0 | 0 |
| Period Title: Lead-In | ||||
| STARTED | 0 | 0 | 65 | 67 |
| COMPLETED | 0 | 0 | 1 | 2 |
| NOT COMPLETED | 0 | 0 | 64 | 65 |
Baseline Characteristics
| Arm/Group Title | Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-in) | Sunitinib + Erlotinib | Erlotinib + Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules once daily (QD) for 28 days each cycle with exception of Cycle 2 (27 days) and Erlotinib 150 mg oral tablets QD for 28 days each cycle with exception of Cycle 1 (35 days). | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1, Arm A or 13 days in Cycle 1, Arm B) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1, Arm A or 26 days in Cycle 1, Arm B) | Sunitinib oral capsules, 37.5 mg QD in a continuous regimen, expressed in 4-week cycles and Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. | Total of all reporting groups |
| Overall Participants | 13 | 17 | 65 | 67 | 162 |
| Age, Customized (participants) [Number] | |||||
| Less than 65 years |
7
53.8%
|
10
58.8%
|
47
72.3%
|
43
64.2%
|
107
66%
|
| Greater than or equal to 65 years |
6
46.2%
|
7
41.2%
|
17
26.2%
|
24
35.8%
|
54
33.3%
|
| Unknown or Not Collected |
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
1
0.6%
|
| Sex/Gender, Customized (participants) [Number] | |||||
| Female |
6
46.2%
|
6
35.3%
|
25
38.5%
|
22
32.8%
|
59
36.4%
|
| Male |
7
53.8%
|
11
64.7%
|
39
60%
|
45
67.2%
|
102
63%
|
| Unknown or Not Collected |
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
1
0.6%
|
Outcome Measures
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS=time from randomization date to date of first documentation of progressive disease (PD; defined as greater than or equal to [≥]20% increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since first dose or appearance of ≥1 new lesions) or death on-study due to any cause, whichever occurred first based on third party independent imaging review laboratory assessment. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02. Used 7.02 days as it equals 365 days per year divided by 52 weeks per year. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FA):all participants in randomized phase randomized with study medication assignment designated according to initial randomization, regardless of whether participants actually received study medication or received different medication from what they were randomized. |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (95% Confidence Interval) [Weeks] |
12.3
|
8.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Sample size for randomized portion of study determined based on these assumptions: median PFS (erlotinib)=10 weeks, accrual time=12 months. With 6 months follow-up, study was powered to detect a difference in PFS of 5 weeks. 1-sided log rank test comparing the 2 treatment groups with 115 events of PD or death among a target sample size of 126 participants (63 per group) achieved 80% power at a 10% significance level to detect a 50% improvement in PFS from 10 to 15 weeks. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3206 |
| Comments | Primary analysis was based on an unstratified 1-sided log rank test with alpha=0.1 | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.898 | |
| Confidence Interval |
(2-Sided) 80% 0.575 to 1.404 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Objective Response |
|---|---|
| Description | Objective Response Rate (ORR)=participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST,Version 1.0) based on third party independent imaging review laboratory assessment. A CR was defined as the disappearance of all target lesions that persisted on repeat imaging study at least 4 weeks after initial documentation of response. A PR was defined as a ≥30% decrease in sum of longest dimensions of target lesions taking as a reference the baseline sum longest dimensions. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Number (95% Confidence Interval) [Percentage of Participants] |
4.62
35.5%
|
2.99
17.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | 95% confidence interval (CI) calculated based on f-distribution | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6251 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
| Estimated Value | 1.546 | |
| Confidence Interval |
(2-Sided) 95% 0.267 to 8.954 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Tumor Progression (TTP) |
|---|---|
| Description | TTP was defined as the time from date of randomization to first documentation of PD based on third party independent imaging review laboratory assessment. TTP was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (95% Confidence Interval) [Weeks] |
12.3
|
10.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3732 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.921 | |
| Confidence Interval |
(2-Sided) 95% 0.572 to 1.485 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Response (DR) |
|---|---|
| Description | DR was defined as time from first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of PD or death on-study due to any cause, whichever occurred first. DR was calculated as (first date of PD or death minus first date of CR or PR that was subsequently confirmed plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA subset of participants with a confirmed objective response were to be analyzed. As only 3 and 2 responses were observed, duration of response was not analyzed. |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 0 | 0 |
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as time from date of randomization to date of death due to any cause. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive. |
| Time Frame | From randomization until death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (95% Confidence Interval) [Months] |
8.2
|
7.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6171 |
| Comments | p-value from 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.066 | |
| Confidence Interval |
(2-Sided) 95% 0.705 to 1.612 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Surviving at 1 Year |
|---|---|
| Description | Percentage of participants alive at 1 year after date of first administration of study medication. |
| Time Frame | From randomization until death (up until Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Number [Percentage of Participants] |
32
246.2%
|
42
247.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib |
|---|---|---|
| Comments | Percentage of participants surviving at 1 year in the Sunitinib + Erlotinib Treatment Group, estimated using the Kaplan-Meier method | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage |
| Estimated Value | 32 | |
| Confidence Interval |
(2-Sided) 95% 19.7 to 44.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Erlotinib + Placebo |
|---|---|---|
| Comments | Percentage of participants surviving at 1 year in the Erlotinib + Placebo Treatment Group, estimated using the Kaplan-Meier method | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percentage |
| Estimated Value | 42 | |
| Confidence Interval |
(2-Sided) 95% 30.1 to 54.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Time Zero to 24 Hours [AUC(0-24)] of Erlotinib |
|---|---|
| Description | AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of erlotinib |
| Time Frame | Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-in Cohort Arm A: participants received sunitinib QD for 28 days each cycle (27 days in Cycle 1) and erlotinib QD for 28 days each cycle (7 days in Cycle 1) |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm A) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). |
| Measure Participants | 7 |
| Cycle 1, Day 1 |
12.96
(4.00)
|
| Cycle 1, Day 22 |
11.87
(4.35)
|
| Title | AUC(0-24) of Sunitinib |
|---|---|
| Description | AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of sunitinib |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B: participants received sunitinib for 28 days each cycle (13 days in Cycle 1) and erlotinib QD for 28 days each cycle (26 days in Cycle 1). |
| Arm/Group Title | Sunitinib+Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
372.76
(105.21)
|
| Cycle 1, Day 15 |
231.61
(69.42)
|
| Title | AUC(0-24) of SU-012662 (Metabolite of Sunitinib) |
|---|---|
| Description | AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of SU-012662 (metabolite of sunitinib) |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib+Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
50.06
(22.76)
|
| Cycle 1, Day 15 |
99.57
(39.48)
|
| Title | AUC(0-24) of Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | AUC0-24=Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours (0-24) of total drug (sunitinib + SU-012662) |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib+Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
422.93
(123.29)
|
| Cycle 1, Day 15 |
331.45
(88.67)
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Erlotinib |
|---|---|
| Description | |
| Time Frame | Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm A |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm A) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). |
| Measure Participants | 7 |
| Cycle 1, Day 1 |
0.99
(0.48)
|
| Cycle 1, Day 22 |
0.86
(0.37)
|
| Title | Cmax of Sunitinib |
|---|---|
| Description | |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib+Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
21.61
(6.76)
|
| Cycle 1, Day 15 |
13.59
(5.88)
|
| Title | Cmax of SU-012662 (Metabolite of Sunitinib) |
|---|---|
| Description | |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib+Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
3.09
(1.33)
|
| Cycle 1, Day 15 |
6.83
(4.22)
|
| Title | Cmax of Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib+Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
24.51
(7.72)
|
| Cycle 1, Day 15 |
20.09
(7.80)
|
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC0-inf) for Erlotinib |
|---|---|
| Description | AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for erlotinib. It is obtained from AUC from time zero (pre-dose) to last quantifiable concentration(AUC[0-t]) plus AUC from time last quantifiable concentration extrapolated infinite time (AUC[t-inf]) |
| Time Frame | Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose; predose on Days 22 and 23 (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm A; Due to the long half-life of the drug and sample collection just up to 24 hours only, AUC(0-inf) could not be accurately estimated. |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm A) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). |
| Measure Participants | 0 |
| Title | AUC(0-inf) for Sunitinib |
|---|---|
| Description | AUC (0 - inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for sunitinib. It is obtained from AUC(0-t) plus AUC(t-inf) |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B; Due to the long half-life of the drug and sample collection just up to 48 hours only, AUC(0-inf) could not be accurately estimated. |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 0 |
| Title | AUC(0-inf) for SU-012662 (Metabolite of Sunitinib) |
|---|---|
| Description | AUC(0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for SU-012662 (metabolite of sunitinib). It is obtained from AUC(0-t) plus AUC(t-inf) |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B; Due to the long half-life of the drug and sample collection just up to 48 hours only, AUC(0-inf) could not be accurately estimated. |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 0 |
| Title | AUC(0-inf) for Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | AUC(0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf) for total drug (sunitinib + SU-012662). It is obtained from AUC(0-t) plus AUC(t-inf) |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose; predose on Days 15, 16, and 17 (Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B; Due to the long half-life of the drug and sample collection just up to 48 hours only, AUC(0-inf) could not be accurately estimated. |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 0 |
| Title | Plasma Decay Half-life (t1/2) of Erlotinib |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm A; Due to the long half-life of the drug and sample collection just up to 24 hours only, t1/2 could not be accurately estimated. |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm A) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). |
| Measure Participants | 0 |
| Title | Plasma Decay Half-life (t1/2) of Sunitinib |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B; Due to the long half-life of the drug and sample collection just up to 48 hours only, t1/2 could not be accurately estimated. |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 0 |
| Title | Erlotinib Clearance at Steady State After Oral Administration (CL/F) |
|---|---|
| Description | |
| Time Frame | Day 15 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants with calculable data in Original Lead-In; after protocol amendment 3, the study design was modified (steady-state versus single dose), due to the long half-life of the drug, sample collection just up to 24 hours was not sufficient for the calculation of CL/F for Amended Lead-In Arm A. |
| Arm/Group Title | Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-In Arm A) |
|---|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). |
| Measure Participants | 8 | 0 |
| Mean (Standard Deviation) [Liters (L)/hr] |
5.52
(3.65)
|
| Title | Sunitinib Clearance at Steady State After Oral Administration (CL/F) |
|---|---|
| Description | |
| Time Frame | Day 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants with calculable data in Original Lead-In Cohort; after protocol amendment 3, the study design was modified (steady-state versus single dose), due to the long half-life of the drug, sample collection just up to 48 hours was not sufficient for the calculation of CL/F for Amended Lead-In Arm B. |
| Arm/Group Title | Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules once daily (QD) for 28 days each cycle with exception of Cycle 2 (27 days)and Erlotinib 150 mg oral tablets QD for 28 days each cycle with exception of Cycle 1 (35 days). | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 | 0 |
| Mean (Standard Deviation) [L/hr] |
63.28
(13.50)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Erlotinib |
|---|---|
| Description | |
| Time Frame | Days 1 and 22 (Cycle 1) at 0, 1, 2, 4, 6, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm A |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm A) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1). |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
2.00
|
| Cycle 1, Day 22 |
2.00
|
| Title | Tmax for Sunitinib |
|---|---|
| Description | |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
6.00
|
| Cycle 1, Day 15 |
6.00
|
| Title | Tmax for SU-012662 (Metabolite of Sunitinib) |
|---|---|
| Description | |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
4.00
|
| Cycle 1, Day 15 |
4.00
|
| Title | Tmax for Total Drug (Sunitinib + SU-012662) |
|---|---|
| Description | |
| Time Frame | Days 1 and 15 of Cycle 1 at 0, 1, 2, 4, 6, 8, 24 and 48 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Amended Lead-In Cohort Arm B |
| Arm/Group Title | Sunitinib + Erlotinib (Amended Lead-In Arm B) |
|---|---|
| Arm/Group Description | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (13 days in Cycle 1) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (26 days in Cycle 1) |
| Measure Participants | 8 |
| Cycle 1, Day 1 |
6.00
|
| Cycle 1, Day 15 |
5.00
|
| Title | Dose-Corrected Observed Plasma Trough Concentrations (Ctrough) for Erlotinib on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) |
|---|---|
| Description | Ctrough = plasma concentration of erlotinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18. |
| Time Frame | predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed (N)=participants with observations above lower limit of quantification (LLOQ) in Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), Randomized Cohort (Sunitinib + Erlotinib treatment group only); n=number of participants with observations above LLOQ for specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib (All Combined) |
|---|---|
| Arm/Group Description | Combined Data from all participants in the Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), and Randomized Cohort |
| Measure Participants | 45 |
| Cycle 2, Day 1 (n=45) |
1.46
(0.90)
|
| Cycle 3, Day 1 (n=44) |
1.07
(0.76)
|
| Cycle 4, Day 1 (n=31) |
1.11
(0.85)
|
| Cycle 5, Day 1 (n=22) |
1.00
(0.93)
|
| Cycle 6, Day 1 (n=18) |
1.00
(0.80)
|
| Cycle 7, Day 1 (n=15) |
1.16
(1.30)
|
| Cycle 8, Day 1 (n=8) |
0.57
(0.34)
|
| Cycle 9, Day 1 (n=10) |
0.90
(0.68)
|
| Cycle 10, Day 1 (n=6) |
1.52
(1.48)
|
| Cycle 11, Day 1 (n=6) |
1.94
(3.67)
|
| Cycle 12, Day 1 (n=5) |
1.21
(1.18)
|
| Cycle 13, Day 1 (n=3) |
0.75
(0.43)
|
| Title | Dose-Corrected Ctrough for Erlotinib on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) |
|---|---|
| Description | Ctrough = plasma concentration of erlotinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18. |
| Time Frame | predose Day 15 (Cycle1); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed (N)=participants with observations above LLOQ in Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), Randomized Cohort (Sunitinib + Erlotinib treatment group only); n=number of participants with observations above LLOQ for specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib (All Combined) |
|---|---|
| Arm/Group Description | Combined Data from all participants in the Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), and Randomized Cohort |
| Measure Participants | 45 |
| Cycle 1, Day 15 (n=6) |
1.14
(0.92)
|
| Cycle 2, Day 1 (n=45) |
1.46
(0.90)
|
| Cycle 3, Day 1 (n=44) |
1.07
(0.76)
|
| Cycle 4, Day 1 (n=20) |
0.99
(0.71)
|
| Cycle 5, Day 1 (n=16) |
0.98
(0.99)
|
| Cycle 6, Day 1 (n=12) |
1.09
(0.85)
|
| Cycle 7, Day 1 (n=8) |
1.08
(1.13)
|
| Cycle 8, Day 1 (n=3) |
0.80
(0.36)
|
| Cycle 9, Day 1 (n=6) |
0.94
(0.80)
|
| Cycle 10, Day 1 (n=4) |
1.71
(1.73)
|
| Cycle 11, Day 1 (n=3) |
0.53
(0.57)
|
| Cycle 12, Day 1 (n=4) |
1.31
(1.34)
|
| Cycle 13, Day 1 (n=3) |
0.75
(0.43)
|
| Title | Dose-Corrected Ctrough for Sunitinib on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) |
|---|---|
| Description | Ctrough = plasma concentration of sunitinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18. |
| Time Frame | predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed (N)=participants with observations above LLOQ in Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), Randomized Cohort (Sunitinib + Erlotinib treatment group only); n=number of participants with observations above LLOQ for specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib (All Combined) |
|---|---|
| Arm/Group Description | Combined Data from all participants in the Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), and Randomized Cohort |
| Measure Participants | 44 |
| Cycle 2, Day 1 (n=44) |
22.94
(11.34)
|
| Cycle 3, Day 1 (n=43) |
21.48
(9.62)
|
| Cycle 4, Day 1 (n=28) |
19.93
(12.74)
|
| Cycle 5, Day 1 (n=22) |
18.58
(10.47)
|
| Cycle 6, Day 1 (n=19) |
22.07
(13.32)
|
| Cycle 7, Day 1 (n=15) |
24.85
(12.12)
|
| Cycle 8, Day 1 (n=8) |
18.44
(7.35)
|
| Cycle 9, Day 1 (n=9) |
14.81
(7.56)
|
| Cycle 10, Day 1 (n=6) |
17.17
(6.10)
|
| Cycle 11, Day 1 (n=6) |
21.42
(19.10)
|
| Cycle 12, Day 1 (n=4) |
11.67
(4.57)
|
| Cycle 13, Day 1 (n=3) |
19.79
(13.47)
|
| Title | Dose-Corrected Ctrough for Sunitinib on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) |
|---|---|
| Description | Ctrough = plasma concentration of sunitinib prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18. |
| Time Frame | predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed (N)=participants with observations above LLOQ in Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), Randomized Cohort (Sunitinib + Erlotinib treatment group only); n=number of participants with observations above LLOQ for specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib (All Combined) |
|---|---|
| Arm/Group Description | Combined Data from all participants in the Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), and Randomized Cohort |
| Measure Participants | 44 |
| Cycle 1, Day 15 (n=7) |
18.80
(4.27)
|
| Cycle 2, Day 1 (n=44) |
22.94
(11.34)
|
| Cycle 3, Day 1 (n=43) |
21.48
(9.62)
|
| Cycle 4, Day 1 (n=19) |
20.58
(13.96)
|
| Cycle 5, Day 1 (n=16) |
17.26
(9.79)
|
| Cycle 6, Day 1 (n=13) |
20.16
(8.78)
|
| Cycle 7, Day 1 (n=8) |
21.97
(10.21)
|
| Cycle 8, Day 1 (n=4) |
13.56
(6.31)
|
| Cycle 9, Day 1 (n=6) |
15.17
(7.71)
|
| Cycle 10, Day 1 (n=4) |
15.61
(6.45)
|
| Cycle 11, Day 1 (n=3) |
15.24
(6.65)
|
| Cycle 12, Day 1 (n=3) |
11.99
(5.54)
|
| Cycle 13, Day 1 (n=3) |
19.79
(13.47)
|
| Title | Dose-Corrected Ctrough for SU-012662 (Metabolite of Sunitinib) on Day 1 of Cycles 3-13 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) |
|---|---|
| Description | Ctrough = plasma concentration of SU-012662 prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original and Amended Lead-In (Arms A and B) Cohorts predose on Day 1 (Cycles 3-13) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18. |
| Time Frame | predose Day 1 (Cycles 3-13); predose Day 1 (Cycles 1-18) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed (N)=participants with observations above LLOQ in Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), Randomized Cohort (Sunitinib + Erlotinib treatment group only); n=number of participants with observations above LLOQ for specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib (All Combined) |
|---|---|
| Arm/Group Description | Combined Data from all participants in the Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), and Randomized Cohort |
| Measure Participants | 44 |
| Cycle 2, Day 1 (n=44) |
21.02
(8.75)
|
| Cycle 3, Day 1 (n=43) |
19.26
(11.67)
|
| Cycle 4, Day 1 (n=28) |
15.74
(7.88)
|
| Cycle 5, Day 1 (n=22) |
15.38
(6.05)
|
| Cycle 6, Day 1 (n=19) |
15.04
(6.18)
|
| Cycle 7, Day 1 (n=15) |
17.13
(9.34)
|
| Cycle 8, Day 1 (n=8) |
12.50
(3.76)
|
| Cycle 9, Day 1 (n=9) |
12.24
(5.19)
|
| Cycle 10, Day 1 (n=6) |
14.29
(8.84)
|
| Cycle 11, Day 1 (n=6) |
19.35
(21.60)
|
| Cycle 12, Day 1 (n=4) |
11.58
(1.82)
|
| Cycle 13, Day 1 (n=3) |
15.60
(9.96)
|
| Title | Dose-Corrected Ctrough for SU-012662 (Metabolite of Sunitinib) on Day 15 Cycle 1 (Original), Day 1 of Cycle 3 (Original and Amended, Arms A and B), and Day 1 of Cycles 1-18 (Randomized) |
|---|---|
| Description | Ctrough = plasma concentration of SU-012662 prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. Assessed in the Original Cohort predose on Day 15 (Cycle 1, Time Zero) and Day 1 (Cycle 3), in the Amended Lead-In Cohort (Arms A and B) predose on Day 1 (Cycle 3) and in the Randomized Cohort (Sunitinib + Erlotinib treatment group only) predose on Day 1 of Cycles 1-18. |
| Time Frame | predose Day 15 (Cycle 1) and Day 1 (Cycle 3); predose Day 1 (Cycle 3); predose Day 1 (Cycles 1-18) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants analyzed (N)=participants with observations above LLOQ in Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), Randomized Cohort (Sunitinib + Erlotinib treatment group only); n=number of participants with observations above LLOQ for specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib (All Combined) |
|---|---|
| Arm/Group Description | Combined Data from all participants in the Original Lead-In Cohort, Amended Lead-In Cohort (Arms A and B), and Randomized Cohort |
| Measure Participants | 44 |
| Cycle 1, Day 15 (n=7) |
18.08
(6.14)
|
| Cycle 2, Day 1 (n=44) |
21.02
(8.75)
|
| Cycle 3, Day 1 (n=43) |
19.26
(11.67)
|
| Cycle 4, Day 1 (n=19) |
16.41
(7.74)
|
| Cycle 5, Day 1 (n=16) |
15.26
(4.97)
|
| Cycle 6, Day 1 (n=13) |
15.05
(4.95)
|
| Cycle 7, Day 1 (n=8) |
15.99
(5.03)
|
| Cycle 8, Day 1 (n=4) |
12.80
(3.94)
|
| Cycle 9, Day 1 (n=6) |
14.00
(5.59)
|
| Cycle 10, Day 1 (n=4) |
16.44
(10.57)
|
| Cycle 11, Day 1 (n=3) |
11.98
(3.31)
|
| Cycle 12, Day 1 (n=3) |
11.26
(2.08)
|
| Cycle 13, Day 1 (n=3) |
15.60
(9.96)
|
| Title | Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Expression by Immunohistochemistry (IHC) Using 0 Percent [%] Cutoff |
|---|---|
| Description | Percentage of participants with EGFR expression by IHC using a 0% cutoff; Reported as positive, negative, or unmeasured (where positive was greater than 0% of cells demonstrating membranous staining for EGFR). Correlative analysis of EGFR expression was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Positive |
35
269.2%
|
36
211.8%
|
| Negative |
38
292.3%
|
36
211.8%
|
| Unmeasured |
26
200%
|
28
164.7%
|
| Title | PFS in Subgroups That Were Defined by EGFR Expression (Using 0% Cutoff) |
|---|---|
| Description | PFS defined as time in weeks from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in the following subgroups: positive, negative, or unmeasured EGFR expression. EGFR expression was analyzed using a 0% cutoff where positive was greater than 0% of cells demonstrating membranous staining for EGFR. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Positive |
16.0
|
11.7
|
| Negative |
8.1
|
8.5
|
| Unmeasured |
12.3
|
8.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Positive EGFR Expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2247 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio, log |
| Estimated Value | 0.748 | |
| Confidence Interval |
(2-Sided) 95% 0.351 to 1.591 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Negative EGFR Expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6797 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.184 | |
| Confidence Interval |
(2-Sided) 95% 0.581 to 2.414 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Unmeasured EGFR Expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1693 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.632 | |
| Confidence Interval |
(2-Sided) 95% 0.245 to 1.627 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With EGFR Expression by IHC (Using 10% Cutoff) |
|---|---|
| Description | Percentage of participants with EGFR Expression by IHC using a 10% cutoff; Reported as positive (positive values were defined as being greater than 10% of cells demonstrating membranous staining for EGFR), negative, or unmeasured. Correlative analysis of EGFR expression was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Positive |
45
346.2%
|
54
317.6%
|
| Negative |
29
223.1%
|
18
105.9%
|
| Unmeasured |
26
200%
|
28
164.7%
|
| Title | PFS in Subgroups That Were Defined by EGFR Expression (Using 10% Cutoff) |
|---|---|
| Description | PFS defined as time in weeks from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in the following subgroups: positive, negative, or unmeasured EGFR expression. EGFR expression was analyzed using a 10% cutoff where positive was greater than 10% of cells demonstrating membranous staining for EGFR. PFS calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Positive |
16.0
|
10.4
|
| Negative |
8.1
|
8.1
|
| Unmeasured |
12.3
|
8.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Positive EGFR Expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3223 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.864 | |
| Confidence Interval |
(2-Sided) 95% 0.458 to 1.628 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Negative EGFR Expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4608 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.946 | |
| Confidence Interval |
(2-Sided) 95% 0.362 to 2.474 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Unmeasured EGFR Expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1693 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.632 | |
| Confidence Interval |
(2-Sided) 95% 0.245 to 1.627 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With EGFR Gene Copy Number Increase |
|---|---|
| Description | The number of copies corresponding to exon 19 of the EGFR gene was determined by real-time quantitative polymerase chain reaction (PCR). The percentage of participants with EGFR Gene Copy Number Increase (defined as greater than 4 copies) was determined using deoxyribonucleic acid (DNA) from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. Reported as yes, no or unmeasured. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Yes |
0
0%
|
1
5.9%
|
| No |
48
369.2%
|
42
247.1%
|
| Unmeasured |
52
400%
|
57
335.3%
|
| Title | PFS in Subgroups That Were Defined by EGFR Gene Copy Number Increase |
|---|---|
| Description | PFS, defined as time from date of randomization to the date of the first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene copy number increase (reported as yes, no, or unmeasured). The number of copies corresponding to exon 19 of the EGFR gene was determined and an increase was defined as greater than 4 copies. PFS was calculated as (first event date minus randomization date plus 1)/7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Yes |
NA
|
NA
|
| No |
12.3
|
8.8
|
| Unmeasured |
12.0
|
8.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | No EGFR Gene Copy Number Increase | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5526 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.049 | |
| Confidence Interval |
(2-Sided) 95% 0.542 to 2.031 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Unmeasured EGFR Gene Copy Number Increase | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1529 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.715 | |
| Confidence Interval |
(2-Sided) 95% 0.380 to 1.344 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With EGFR Gene Amplification |
|---|---|
| Description | The percentage of participants with EGFR gene amplification (defined as greater than 15) was determined and reported as yes, no, or unmeasured. Correlative analysis of EGFR gene amplification was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Yes |
0
0%
|
0
0%
|
| No |
48
369.2%
|
43
252.9%
|
| Unmeasured |
52
400%
|
57
335.3%
|
| Title | PFS in Subgroups That Were Defined by EGFR Gene Amplification |
|---|---|
| Description | PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene amplification (defined as greater than 15) and reported as no or unmeasured. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| No |
12.3
|
11.7
|
| Unmeasured |
12.0
|
8.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | No EGFR Gene Amplification | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5839 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.078 | |
| Confidence Interval |
(2-Sided) 95% 0.557 to 2.085 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Unmeasured EGFR Gene Amplification | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1529 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.715 | |
| Confidence Interval |
(2-Sided) 95% 0.380 to 1.344 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With EGFR Gene Mutation |
|---|---|
| Description | Mutations in exons 18 through 21 of the EGFR gene were analyzed by high-performance liquid chromatography using DNA from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. The percentage of participants with EGFR mutations categorized as mutated, wild type or indeterminate was reported. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Mutated |
6
46.2%
|
1
5.9%
|
| Wild Type |
32
246.2%
|
28
164.7%
|
| Indeterminate |
62
476.9%
|
70
411.8%
|
| Title | PFS in Subgroups That Were Defined by EGFR Gene Mutation |
|---|---|
| Description | PFS, defined as time from date of randomization to date of first documentation of PD or to death on-study due to any cause, whichever occurred first, in subgroups that were defined by EGFR gene mutation (reported as mutated, wild type, or indeterminate). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Mutated |
19.1
|
NA
|
| Wild Type |
9.0
|
11.7
|
| Indeterminate |
12.0
|
8.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Wild Type EGFR Gene Mutation | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6324 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.160 | |
| Confidence Interval |
(2-Sided) 95% 0.516 to 2.608 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate EGFR Gene Mutation | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2413 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.813 | |
| Confidence Interval |
(2-Sided) 95% 0.464 to 1.424 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With KRAS (V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog) Gene Mutations |
|---|---|
| Description | Mutations in exons 2-3 of the KRAS gene (including codons 12, 13, and 61) were analyzed by high-performance liquid chromatography using DNA from tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. The percentage of participants with KRAS mutations categorized as mutated, wild type or indeterminate was reported. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Mutated |
9
69.2%
|
6
35.3%
|
| Wild Type |
34
261.5%
|
28
164.7%
|
| Indeterminate |
57
438.5%
|
66
388.2%
|
| Title | PFS in Subgroups That Were Defined by KRAS Gene Mutation |
|---|---|
| Description | PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by KRAS gene mutation (reported as mutated, wild type, or indeterminate). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Mutated |
20.1
|
7.5
|
| Wild Type |
9.5
|
12.1
|
| Indeterminate |
12.3
|
8.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Mutated KRAS Gene Mutation | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2077 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.481 | |
| Confidence Interval |
(2-Sided) 95% 0.079 to 2.910 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Wild Type KRAS Gene Mutation | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6439 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.162 | |
| Confidence Interval |
(2-Sided) 95% 0.534 to 2.531 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate KRAS Gene Mutation | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2664 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.825 | |
| Confidence Interval |
(2-Sided) 95% 0.457 to 1.489 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Germline Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Polymorphisms |
|---|---|
| Description | Blood samples were collected at baseline for multiplex reverse transcription (RT) analysis of genes expressing proteins that are targets of sunitinib or involved in angiogenesis or tumor growth to determine expression levels. Percentage of participants with germline VEGFR2 single nucleotide polymorphisms (SNPs) was reported for the following genotype frequencies: homozygous C alleles (C/C), T alleles (T/T), G alleles (G/G), or A alleles (A/A), and the following heterozygous genotypes C/T, G/T, T/A, and G/A. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis - All Population: all participants from lead-in period and Phase 2 (randomized phase) |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | All participants in all phases. |
| Measure Participants | 162 |
| Locus: VEGFR2 / rs1531289; Genotype: C/C |
44.9
345.4%
|
| Locus: VEGFR2 / rs1531289; Genotype: C/T |
45.6
350.8%
|
| Locus: VEGFR2 / rs1531289; Genotype: T/T |
9.6
73.8%
|
| Locus: VEGFR2 / rs2305945; Genotype: G/G |
44.1
339.2%
|
| Locus: VEGFR2 / rs2305945; Genotype: G/T |
47.1
362.3%
|
| Locus: VEGFR2 / rs2305945; Genotype: T/T |
8.8
67.7%
|
| Locus VEGFR2 / rs1870377; Genotype: T/T |
53.7
413.1%
|
| Locus VEGFR2 / rs1870377; Genotype: T/A |
39.7
305.4%
|
| Locus VEGFR2 / rs1870377; Genotype: A/A |
6.6
50.8%
|
| Locus: VEGFR2 / rs2305948; Genotype: C/C |
81.6
627.7%
|
| Locus: VEGFR2 / rs2305948; Genotype: C/T |
17.6
135.4%
|
| Locus: VEGFR2 / rs2305948; Genotype: T/T |
0.7
5.4%
|
| Locus: VEGFR2 / rs7692791; Genotype: C/C |
19.9
153.1%
|
| Locus: VEGFR2 / rs7692791; Genotype: C/T |
50.7
390%
|
| Locus: VEGFR2 / rs7692791; Genotype: T/T |
29.4
226.2%
|
| Locus: VEGFR2 / rs35636987; Genotype: C/C |
100
769.2%
|
| Locus: VEGFR2 / rs7667298; Genotype: C/C |
27.2
209.2%
|
| Locus: VEGFR2 / rs7667298; Genotype: C/T |
50.0
384.6%
|
| Locus: VEGFR2 / rs7667298; Genotype: T/T |
22.8
175.4%
|
| Locus: VEGFR2 / rs41408948; Genotype: G/A |
57.4
441.5%
|
| Locus: VEGFR2 / rs41408948; Genotype: A/A |
36.0
276.9%
|
| Locus: VEGFR2 / rs41408948; Genotype: G/G |
6.6
50.8%
|
| Locus: VEGFR2 / rs2071559; Genotype: G/G |
26.5
203.8%
|
| Locus: VEGFR2 / rs2071559; Genotype: G/A |
47.8
367.7%
|
| Locus: VEGFR2 / rs2071559; Genotype: A/A |
25.7
197.7%
|
| Title | PFS in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms |
|---|---|
| Description | PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by VEGFR2 polymorphisms. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per Protocol Caucasian Population: all Caucasian participants in randomized phase who received at least 1 dose of study medication (either erlotinib or blinded medication), with treatment assignments designated according to actual study medication received |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 53 | 50 |
| Locus: VEGFR2/rs1531289 Genotype: C/C |
9.00
|
8.10
|
| Locus: VEGFR2/rs1531289 Genotype: C/T |
17.00
|
8.00
|
| Locus: VEGFR2/rs1531289 Genotype: T/T |
NA
|
13.00
|
| Locus: VEGFR2/rs2305945 Genotype: G/G |
17.00
|
12.30
|
| Locus: VEGFR2/rs2305945 Genotype: G/T |
9.00
|
7.80
|
| Locus: VEGFR2/rs2305945 Genotype: T/T |
20.50
|
NA
|
| Locus: VEGFR2/rs1870377 Genotype: T/T |
8.10
|
8.00
|
| Locus: VEGFR2/rs1870377 Genotype: T/A |
17.00
|
8.00
|
| Locus: VEGFR2/rs1870377 Genotype: A/A |
NA
|
20.40
|
| Locus: VEGFR2/rs2305948 Genotype: C/C |
12.00
|
8.00
|
| Locus: VEGFR2/rs2305948 Genotype: C/T |
12.30
|
8.00
|
| Locus: VEGFR2/rs2305948 Genotype: T/T |
NA
|
12.10
|
| Locus: VEGFR2/rs7692791 Genotype: C/C |
12.00
|
7.70
|
| Locus: VEGFR2/rs7692791 Genotype: C/T |
9.00
|
8.50
|
| Locus: VEGFR2/rs7692791 Genotype: T/T |
16.00
|
7.70
|
| Locus: VEGFR2/rs35636987 Genotype: C/C |
12.30
|
8.00
|
| Locus: VEGFR2/rs7667298 Genotype: C/C |
12.00
|
8.05
|
| Locus: VEGFR2/rs7667298 Genotype: C/T |
17.00
|
7.80
|
| Locus: VEGFR2/rs7667298 Genotype: T/T |
9.50
|
12.80
|
| Locus: VEGFR2/rs41408948 Genotype: G/G |
12.00
|
11.70
|
| Locus: VEGFR2/rs41408948 Genotype: G/A |
17.00
|
7.75
|
| Locus: VEGFR2/rs41408948 Genotype: A/A |
13.45
|
13.60
|
| Locus: VEGFR2/rs2071559 Genotype: G/G |
9.50
|
12.80
|
| Locus: VEGFR2/rs2071559 Genotype: G/A |
17.00
|
7.80
|
| Locus: VEGFR2/rs2071559 Genotype: A/A |
8.10
|
8.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1531289 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7423 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.130 | |
| Confidence Interval |
(2-Sided) 95% 0.541 to 2.360 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1531289 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1570 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.598 | |
| Confidence Interval |
(2-Sided) 95% 0.290 to 1.236 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1531289 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7954 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.794 | |
| Confidence Interval |
(2-Sided) 95% 0.131 to 4.819 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305945 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6210 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.833 | |
| Confidence Interval |
(2-Sided) 95% 0.401 to 1.732 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305945 Genotype: G/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5268 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.794 | |
| Confidence Interval |
(2-Sided) 95% 0.385 to 1.640 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1870377 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9753 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.011 | |
| Confidence Interval |
(2-Sided) 95% 0.504 to 2.027 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1870377 Genotype: T/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0141 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.378 | |
| Confidence Interval |
(2-Sided) 95% 0.168 to 0.850 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1870377 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5596 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.236 | |
| Confidence Interval |
(2-Sided) 95% 0.139 to 35.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305948 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2788 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.738 | |
| Confidence Interval |
(2-Sided) 95% 0.422 to 1.288 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305948 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8971 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.075 | |
| Confidence Interval |
(2-Sided) 95% 0.352 to 3.286 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7692791 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6559 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.775 | |
| Confidence Interval |
(2-Sided) 95% 0.251 to 2.388 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7692791 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8563 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.939 | |
| Confidence Interval |
(2-Sided) 95% 0.466 to 1.889 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7692791 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.668 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.382 | |
| Confidence Interval |
(2-Sided) 95% 0.130 to 1.120 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs35636987 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3681 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.800 | |
| Confidence Interval |
(2-Sided) 95% 0.488 to 1.309 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7667298 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7520 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.860 | |
| Confidence Interval |
(2-Sided) 95% 0.331 to 2.237 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7667298 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0833 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.551 | |
| Confidence Interval |
(2-Sided) 95% 0.276 to 1.098 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7667298 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4772 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.564 | |
| Confidence Interval |
(2-Sided) 95% 0.444 to 5.506 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs41408948 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9235 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.034 | |
| Confidence Interval |
(2-Sided) 95% 0.522 to 2.048 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs41408948 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0845 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.501 | |
| Confidence Interval |
(2-Sided) 95% 0.223 to 1.126 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs41408948 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5493 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.724 | |
| Confidence Interval |
(2-Sided) 95% 0.284 to 10.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2071559 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5210 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.400 | |
| Confidence Interval |
(2-Sided) 95% 0.492 to 3.987 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2071559 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0854 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.538 | |
| Confidence Interval |
(2-Sided) 95% 0.261 to 1.108 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2071559 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9198 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.953 | |
| Confidence Interval |
(2-Sided) 95% 0.365 to 2.489 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) in Subgroups That Were Defined by Germline VEGFR2 Polymorphisms |
|---|---|
| Description | OS, defined as time from date of randomization to date of death due to any cause, in subgroups that were defined by VEGFR2 polymorphisms. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4. |
| Time Frame | From randomization until death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per Protocol Caucasian Population |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 53 | 50 |
| Locus: VEGFR2/rs1531289 Genotype: C/C |
8.20
|
6.20
|
| Locus: VEGFR2/rs1531289 Genotype: C/T |
6.40
|
5.30
|
| Locus: VEGFR2/rs1531289 Genotype: T/T |
11.60
|
16.50
|
| Locus: VEGFR2/rs2305945 Genotype: G/G |
8.00
|
5.50
|
| Locus: VEGFR2/rs2305945 Genotype: G/T |
6.25
|
7.60
|
| Locus: VEGFR2/rs2305945 Genotype: T/T |
NA
|
NA
|
| Locus: VEGFR2/rs1870377 Genotype: T/T |
6.40
|
10.00
|
| Locus: VEGFR2/rs1870377 Genotype: T/A |
8.00
|
4.70
|
| Locus: VEGFR2/rs1870377 Genotype: A/A |
NA
|
NA
|
| Locus: VEGFR2/rs2305948 Genotype: C/C |
8.40
|
10.00
|
| Locus: VEGFR2/rs2305948 Genotype: C/T |
5.80
|
4.90
|
| Locus: VEGFR2/rs2305948 Genotype: T/T |
NA
|
NA
|
| Locus: VEGFR2/rs7692791 Genotype: C/C |
6.40
|
7.60
|
| Locus: VEGFR2/rs7692791 Genotype: C/T |
9.30
|
5.80
|
| Locus: VEGFR2/rs7692791 Genotype: T/T |
6.30
|
10.00
|
| Locus: VEGFR2/rs35636987 Genotype: C/C |
8.00
|
6.80
|
| Locus: VEGFR2/rs7667298 Genotype: C/C |
9.30
|
13.40
|
| Locus: VEGFR2/rs7667298 Genotype: C/T |
6.65
|
4.90
|
| Locus: VEGFR2/rs7667298 Genotype: T/T |
11.30
|
9.60
|
| Locus: VEGFR2/rs41408948 Genotype: G/G |
6.40
|
8.40
|
| Locus: VEGFR2/rs41408948 Genotype: G/A |
8.00
|
4.40
|
| Locus: VEGFR2/rs41408948 Genotype: A/A |
11.30
|
9.55
|
| Locus: VEGFR2/rs2071559 Genotype: G/G |
11.30
|
8.60
|
| Locus: VEGFR2/rs2071559 Genotype: G/A |
6.90
|
4.90
|
| Locus: VEGFR2/rs2071559 Genotype: A/A |
9.30
|
13.40
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1531289 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9486 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.977 | |
| Confidence Interval |
(2-Sided) 95% 0.473 to 2.014 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1531289 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9084 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.961 | |
| Confidence Interval |
(2-Sided) 95% 0.487 to 1.897 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1531289 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2009 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.876 | |
| Confidence Interval |
(2-Sided) 95% 0.534 to 15.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305845 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7863 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.098 | |
| Confidence Interval |
(2-Sided) 95% 0.554 to 2.175 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEFR2/rs2305945 Genotype: G/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5267 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.243 | |
| Confidence Interval |
(2-Sided) 95% 0.633 to 2.442 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305945 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6240 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.550 | |
| Confidence Interval |
(2-Sided) 95% 0.049 to 6.208 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEFR/rs1870377 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4882 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.254 | |
| Confidence Interval |
(2-Sided) 95% 0.660 to 2.384 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1870377 Genotype: T/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1307 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.587 | |
| Confidence Interval |
(2-Sided) 95% 0.290 to 1.189 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs1870377 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5596 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.236 | |
| Confidence Interval |
(2-Sided) 95% 0.139 to 35.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305948 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7966 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.073 | |
| Confidence Interval |
(2-Sided) 95% 0.628 to 1.833 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2305948 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9224 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.954 | |
| Confidence Interval |
(2-Sided) 95% 0.366 to 2.484 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7692791 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9317 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.047 | |
| Confidence Interval |
(2-Sided) 95% 0.363 to 3.025 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7692791 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8696 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.057 | |
| Confidence Interval |
(2-Sided) 95% 0.546 to 2.044 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7692791 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8694 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.075 | |
| Confidence Interval |
(2-Sided) 95% 0.453 to 2.554 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs3563987 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8708 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.039 | |
| Confidence Interval |
(2-Sided) 95% 0.654 to 1.652 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7667298 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7667 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.157 | |
| Confidence Interval |
(2-Sided) 95% 0.442 to 3.026 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7667298 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3822 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.755 | |
| Confidence Interval |
(2-Sided) 95% 0.401 to 1.422 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs7667298 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5089 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.419 | |
| Confidence Interval |
(2-Sided) 95% 0.498 to 4.040 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs41408948 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3944 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.326 | |
| Confidence Interval |
(2-Sided) 95% 0.691 to 2.544 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs41408948 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3103 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.692 | |
| Confidence Interval |
(2-Sided) 95% 0.339 to 1.416 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs41408948 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8942 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.857 | |
| Confidence Interval |
(2-Sided) 95% 0.089 to 8.294 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2071559 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6650 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.240 | |
| Confidence Interval |
(2-Sided) 95% 0.466 to 3.304 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2071559 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4415 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.779 | |
| Confidence Interval |
(2-Sided) 95% 0.412 to 1.475 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: VEGFR2/rs2071559 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4682 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.458 | |
| Confidence Interval |
(2-Sided) 95% 0.523 to 4.060 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Germline Platelet-derived Growth Factor Receptor Beta (PDGFRB) Polymorphisms |
|---|---|
| Description | Blood samples were collected at baseline for multiplex RT analysis of genes expressing proteins that are targets of sunitinib or involved in angiogenesis or tumor growth to determine expression levels. Percentage of participants with germline PDGFRB SNPs was reported for the following genotype frequencies: homozygous C alleles (C/C), T alleles (T/T), G alleles (G/G), or A alleles (A/A), and the following heterozygous genotypes C/T, A/T, A/G, T/C, T/G, G/C, C/A and G/A. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis - All Population |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | All participants in all phases |
| Measure Participants | 162 |
| Locus: PDGFRB / rs2304060 Genotype:C/C |
21.3
163.8%
|
| Locus: PDGFRB / rs2304060 Genotype: C/A |
52.9
406.9%
|
| Locus: PDGFRB / rs2304060 Genotype: A/A |
25.7
197.7%
|
| Locus: PDGFRB / rs17656204 Genotype: C/C |
48.5
373.1%
|
| Locus: PDGFRB / rs17656204 Genotype: C/T |
44.1
339.2%
|
| Locus: PDGFRB / rs17656204 Genotype: T/T |
7.4
56.9%
|
| Locus: PDGFRB / rs2304061 Genotype: G/G |
51.9
399.2%
|
| Locus: PDGFRB / rs2304061 Genotype: G/A |
44.4
341.5%
|
| Locus: PDGFRB / rs2304061 Genotype: A/A |
3.7
28.5%
|
| Locus: PDGFRB / rs1077724 Genotype: A/A |
43.4
333.8%
|
| Locus: PDGFRB / rs1077724 Genotype: A/T |
46.3
356.2%
|
| Locus: PDGFRB / rs1077724 Genotype: T/T |
10.3
79.2%
|
| Locus: PDGFRB / rs919751 Genotype: A/A |
46.3
356.2%
|
| Locus: PDGFRB / rs919751 Genotype: A/G |
39.0
300%
|
| Locus: PDGFRB / rs919751 Genotype: G/G |
14.7
113.1%
|
| Locus: PDGFRB / rs2304058 Genotype: G/G |
25.7
197.7%
|
| Locus: PDGFRB / rs2304058 Genotype: G/C |
49.3
379.2%
|
| Locus: PDGFRB / rs2304058 Genotype: C/C |
25.0
192.3%
|
| Locus: PDGFRB / rs1864972 Genotype: G/G |
41.2
316.9%
|
| Locus: PDGFRB / rs1864972 Genotype: G/A |
41.9
322.3%
|
| Locus: PDGFRB / rs1864972 Genotype: A/A |
16.9
130%
|
| Locus: PDGFRB / rs3733678 Genotype: G/G |
80.1
616.2%
|
| Locus: PDGFRB / rs3733678 Genotype: G/A |
19.9
153.1%
|
| Locus: PDGFRB / rs246396 Genotype: T/T |
70.6
543.1%
|
| Locus: PDGFRB / rs246396 Genotype: T/C |
27.2
209.2%
|
| Locus: PDGFRB / rs246396 Genotype: C/C |
2.2
16.9%
|
| Locus: PDGFRB / rs34586048 Genotype: C/C |
100
769.2%
|
| Locus: PDGFRB / rs11740355 Genotype: T/T |
80.9
622.3%
|
| Locus: PDGFRB / rs11740355 Genotype: T/G |
18.4
141.5%
|
| Locus: PDGFRB / rs11740355 Genotype: G/G |
0.7
5.4%
|
| Locus: PDGFRB / rs740751 Genotype: C/C |
41.2
316.9%
|
| Locus: PDGFRB / rs740751 Genotype: C/T |
41.2
316.9%
|
| Locus: PDGFRB / rs740751 Genotype: T/T |
17.6
135.4%
|
| Locus: PDGFRB / rs4705415 Genotype: G/G |
36.0
276.9%
|
| Locus: PDGFRB / rs4705415 Genotype: G/A |
44.1
339.2%
|
| Locus: PDGFRB / rs4705415 Genotype: A/A |
19.9
153.1%
|
| Locus: PDGFRB / rs3776075 Genotype: T/T |
22.8
175.4%
|
| Locus: PDGFRB / rs3776075 Genotype: T/G |
56.6
435.4%
|
| Locus: PDGFRB / rs3776075 Genotype: G/G |
20.6
158.5%
|
| Locus: PDGFRB / rs17708574 Genotype: G/G |
79.4
610.8%
|
| Locus: PDGFRB / rs17708574 Genotype: G/A |
17.6
135.4%
|
| Locus: PDGFRB / rs17708574 Genotype: A/A |
2.9
22.3%
|
| Locus: PDGFRB / rs10063714 Genotype: T/T |
76.5
588.5%
|
| Locus: PDGFRB / rs10063714 Genotype: T/A |
22.1
170%
|
| Locus: PDGFRB / rs10063714 Genotype: A/A |
1.5
11.5%
|
| Locus: PDGFRB / rs3776081 Genotype: A/A |
39.0
300%
|
| Locus: PDGFRB / rs3776081 Genotype: A/G |
47.1
362.3%
|
| Locus: PDGFRB / rs3776081 Genotype: G/G |
14.0
107.7%
|
| Locus: PDGFRB / rs2007637 Genotype: G/G |
79.4
610.8%
|
| Locus: PDGFRB / rs2007637 Genotype: G/A |
19.1
146.9%
|
| Locus: PDGFRB / rs2007637 Genotype: A/A |
1.5
11.5%
|
| Locus: PDGFRB / rs2302273 Genotype: G/G |
56.0
430.8%
|
| Locus: PDGFRB / rs2302273 Genotype: G/A |
38.1
293.1%
|
| Locus: PDGFRB / rs2302273 Genotype: A/A |
6.0
46.2%
|
| Title | PFS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms |
|---|---|
| Description | PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by PDGFRB polymorphisms. PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per Protocol Caucasian Population |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 53 | 50 |
| Locus: PDGFRB/rs2304060 Genotype: C/C |
12.30
|
19.20
|
| Locus: PDGFRB/rs2304060 Genotype: C/A |
9.00
|
8.00
|
| Locus: PDGFRB/rs2304060 Genotype: A/A |
12.00
|
7.90
|
| Locus: PDGFRB/rs17656204 Genotype: C/C |
16.00
|
8.00
|
| Locus: PDGFRB/rs17656204 Genotype: C/T |
17.00
|
8.00
|
| Locus: PDGFRB/rs17656204 Genotype: T/T |
8.65
|
NA
|
| Locus: PDGFRB/rs2304061 Genotype: G/G |
19.50
|
7.80
|
| Locus: PDGFRB/rs2304061 Genotype: G/A |
7.80
|
8.10
|
| Locus: PDGFRB/rs2304061 Genotype: A/A |
10.90
|
NA
|
| Locus: PDGFRB/rs1077724 Genotype: A/A |
12.00
|
8.00
|
| Locus: PDGFRB/rs1077724 Genotype: A/T |
17.00
|
7.85
|
| Locus: PDGFRB/rs1077724 Genotype: T/T |
12.30
|
19.20
|
| Locus: PDGFRB/rs919751 Genotype: A/A |
9.50
|
11.70
|
| Locus: PDGFRB/rs919751 Genotype: A/G |
12.00
|
7.85
|
| Locus: PDGFRB/rs919751 Genotype: G/G |
19.50
|
7.70
|
| Locus: PDGFRB/rs2304058 Genotype: G/G |
19.50
|
6.35
|
| Locus: PDGFRB/rs2304058 Genotype: G/C |
9.00
|
8.00
|
| Locus: PDGFRB/rs2304058 Genotype: C/C |
12.30
|
8.50
|
| Locus: PDGFRB/rs1864975 Genotype: G/G |
20.10
|
7.85
|
| Locus: PDGFRB/rs1864975 Genotype: G/A |
8.10
|
8.00
|
| Locus: PDGFRB/rs1864975 Genotype: A/A |
12.30
|
8.10
|
| Locus: PDGFRB/rs3733678 Genotype: G/G |
12.00
|
8.00
|
| Locus: PDGFRB/rs3733678 Genotype: G/A |
20.50
|
NA
|
| Locus: PDGFRB/rs246396 Genotype: T/T |
16.00
|
8.00
|
| Locus: PDGFRB/rs246396 Genotype: T/C |
7.80
|
8.10
|
| Locus: PDGFRB/rs246396 Genotype: C/C |
12.30
|
8.00
|
| Locus: PDGFRB/rs34586048 Genotype: C/C |
12.30
|
8.00
|
| Locus: PDGFRB/rs11740355 Genotype: T/T |
12.30
|
8.50
|
| Locus: PDGFRB/rs11740355 Genotype: T/G |
16.00
|
7.40
|
| Locus: PDGFRB/rs11740355 Genotype: G/G |
7.80
|
NA
|
| Locus: PDGFRB/rs740751 Genotype: C/C |
20.10
|
8.00
|
| Locus: PDGFRB/rs740751 Genotype: C/T |
8.10
|
8.00
|
| Locus: PDGFRB/rs740751 Genotype: T/T |
12.30
|
8.10
|
| Locus: PDGFRB/rs4705415 Genotype: G/G |
19.10
|
11.70
|
| Locus: PDGFRB/rs4705415 Genotype: G/A |
8.10
|
7.90
|
| Locus: PDGFRB/rs4705415 Genotype: A/A |
19.50
|
7.70
|
| Locus: PDGFRB/rs3776075 Genotype: T/T |
16.00
|
7.50
|
| Locus: PDGFRB/rs3776075 Genotype: T/G |
12.00
|
8.05
|
| Locus: PDGFRB/rs3776075 Genotype: G/G |
NA
|
10.10
|
| Locus: PDGFRB/rs17708574 Genotype: G/G |
12.30
|
8.05
|
| Locus: PDGFRB/rs17708574 Genotype: G/A |
9.00
|
7.90
|
| Locus: PDGFRB/rs10063714 Genotype: T/T |
12.00
|
8.00
|
| Locus: PDGFRB/rs10063714 Genotype: T/A |
20.50
|
19.20
|
| Locus: PDGFRB/rs3776081 Genotype: A/A |
19.50
|
7.70
|
| Locus: PDGFRB/rs3776081 Genotype: A/G |
12.00
|
8.10
|
| Locus: PDGFRB/rs3776081 Genotype: G/G |
NA
|
10.10
|
| Locus: PDGFRB/rs2007637 Genotype: G/G |
16.00
|
8.00
|
| Locus: PDGFRB/rs2007637 Genotype: G/A |
12.30
|
12.80
|
| Locus: PDGFRB/rs2007637 Genotype: A/A |
4.30
|
52.00
|
| Locus: PDGFRB/rs2302273 Genotype: G/G |
19.50
|
10.15
|
| Locus: PDGFRB/rs2302273 Genotype: G/A |
9.50
|
8.00
|
| Locus: PDGFRB/rs2302273 Genotype: A/A |
NA
|
10.10
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304060 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7301 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.289 | |
| Confidence Interval |
(2-Sided) 95% 0.304 to 5.470 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | PDGFRB/rs2304060 C/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5013 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.788 | |
| Confidence Interval |
(2-Sided) 95% 0.390 to 1.592 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304060 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3680 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.686 | |
| Confidence Interval |
(2-Sided) 95% 0.298 to 1.578 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17656204 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3804 |
| Comments | 2-sided, unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.738 | |
| Confidence Interval |
(2-Sided) 95% 0.371 to 1.467 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17656204 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1507 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.570 | |
| Confidence Interval |
(2-Sided) 95% 0.261 to 1.247 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus PDGFRB/rs17656204 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0772 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304061 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2149 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.660 | |
| Confidence Interval |
(2-Sided) 95% 0.339 to 1.284 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/RS2304061 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9491 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.026 | |
| Confidence Interval |
(2-Sided) 95% 0.466 to 2.260 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1077724 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8114 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.917 | |
| Confidence Interval |
(2-Sided) 95% 0.447 to 1.881 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1077724 Genotype: A/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1379 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.577 | |
| Confidence Interval |
(2-Sided) 95% 0.273 to 1.221 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1077724 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5341 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.859 | |
| Confidence Interval |
(2-Sided) 95% 0.256 to 13.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs919751 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8564 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.932 | |
| Confidence Interval |
(2-Sided) 95% 0.431 to 2.014 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs919751 Genotype: A/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5766 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.797 | |
| Confidence Interval |
(2-Sided) 95% 0.355 to 1.788 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs919751 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2043 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.467 | |
| Confidence Interval |
(2-Sided) 95% 0.140 to 1.557 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304058 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1626 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.531 | |
| Confidence Interval |
(2-Sided) 95% 0.214 to 1.317 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304058 Genotype: G/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9680 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.986 | |
| Confidence Interval |
(2-Sided) 95% 0.484 to 2.006 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304058 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3587 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.573 | |
| Confidence Interval |
(2-Sided) 95% 0.171 to 1.920 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1864972 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4635 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.742 | |
| Confidence Interval |
(2-Sided) 95% 0.331 to 1.662 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1864972 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9834 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.992 | |
| Confidence Interval |
(2-Sided) 95% 0.476 to 2.069 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1864972 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1764 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.353 | |
| Confidence Interval |
(2-Sided) 95% 0.072 to 1.725 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3733678 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2018 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.715 | |
| Confidence Interval |
(2-Sided) 95% 0.422 to 1.209 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3733678 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4592 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.850 | |
| Confidence Interval |
(2-Sided) 95% 0.354 to 9.673 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs246396 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1593 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.665 | |
| Confidence Interval |
(2-Sided) 95% 0.373 to 1.184 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs246396 Genotype: T/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5897 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.327 | |
| Confidence Interval |
(2-Sided) 95% 0.469 to 3.755 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs34586048 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3681 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.800 | |
| Confidence Interval |
(2-Sided) 95% 0.488 to 1.309 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs11740355 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3235 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.752 | |
| Confidence Interval |
(2-Sided) 95% 0.423 to 1.336 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs11740355 Genotype: T/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7463 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.845 | |
| Confidence Interval |
(2-Sided) 95% 0.303 to 2.355 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: rs740751 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4179 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.724 | |
| Confidence Interval |
(2-Sided) 95% 0.330 to 1.593 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs740751 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9423 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.973 | |
| Confidence Interval |
(2-Sided) 95% 0.462 to 2.050 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs7407451 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1764 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.353 | |
| Confidence Interval |
(2-Sided) 95% 0.072 to 1.725 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs4705415 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2352 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.549 | |
| Confidence Interval |
(2-Sided) 95% 0.201 to 1.501 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs4705415 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9674 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.986 | |
| Confidence Interval |
(2-Sided) 95% 0.485 to 2.003 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs4705415 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3524 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.629 | |
| Confidence Interval |
(2-Sided) 95% 0.235 to 1.686 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776075 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6652 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.809 | |
| Confidence Interval |
(2-Sided) 95% 0.308 to 2.124 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776075 Genotype: T/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5931 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.839 | |
| Confidence Interval |
(2-Sided) 95% 0.436 to 1.618 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776075 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2625 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.475 | |
| Confidence Interval |
(2-Sided) 95% 0.125 to 1.813 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 37
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17708574 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2168 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.704 | |
| Confidence Interval |
(2-Sided) 95% 0.400 to 1.239 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 38
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17708574 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9802 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.987 | |
| Confidence Interval |
(2-Sided) 95% 0.353 to 2.759 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 39
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs10063714 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1145 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.652 | |
| Confidence Interval |
(2-Sided) 95% 0.378 to 1.122 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 40
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs10063714 Genotype: T/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7725 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.192 | |
| Confidence Interval |
(2-Sided) 95% 0.360 to 3.946 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 41
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776081 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3286 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.687 | |
| Confidence Interval |
(2-Sided) 95% 0.321 to 1.473 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 42
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776081 Genotype: A/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9480 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.976 | |
| Confidence Interval |
(2-Sided) 95% 0.470 to 2.028 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 43
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776081 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3844 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.531 | |
| Confidence Interval |
(2-Sided) 95% 0.125 to 2.282 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 44
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2007637 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1373 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.662 | |
| Confidence Interval |
(2-Sided) 95% 0.381 to 1.153 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 45
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2007637 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8586 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.114 | |
| Confidence Interval |
(2-Sided) 95% 0.339 to 3.667 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 46
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2302273 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8478 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.935 | |
| Confidence Interval |
(2-Sided) 95% 0.470 to 1.861 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 47
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2302273 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2445 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.634 | |
| Confidence Interval |
(2-Sided) 95% 0.287 to 1.401 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 48
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2302273 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9191 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.155 | |
| Confidence Interval |
(2-Sided) 95% 0.072 to 18.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | OS in Subgroups That Were Defined by Germline PDGFRB Polymorphisms |
|---|---|
| Description | OS, defined as time from date of randomization to date of death due to any cause, in subgroups that were defined by PDGFRB polymorphisms. OS was calculated as (date of death minus date of randomization plus 1) divided by 30.4. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per Protocol Caucasian Population |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 53 | 50 |
| Locus: PDGFRB/rs2304060 Genotype: C/C |
12.80
|
9.60
|
| Locus: PDGFRB/rs2304060 Genotype: C/A |
8.20
|
6.20
|
| Locus: PDGFRB/rs2304060 Genotype: A/A |
5.70
|
5.60
|
| Locus: PDGFRB/rs17656204 Genotype: C/C |
8.00
|
5.90
|
| Locus: PDGFRB/rs17656204 Genotype: C/T |
8.20
|
7.60
|
| Locus: PDGFRB/rs17656204 Genotype: T/T |
6.40
|
NA
|
| Locus: PDGFRB/rs2304061 Genotype: G/G |
6.65
|
4.75
|
| Locus: PDGFRB/rs2304061 Genotype: G/A |
8.40
|
9.60
|
| Locus: PDGFRB/rs2304061 Genotype: A/A |
9.00
|
NA
|
| Locus: PDGFRB/rs1077724 Genotype: A/A |
6.30
|
5.90
|
| Locus: PDGFRB/rs1077724 Genotype: A/T |
9.70
|
6.20
|
| Locus: PDGFRB/rs1077724 Genotype: T/T |
7.25
|
NA
|
| Locus: PDGFRB/rs919751 Genotype: A/A |
8.00
|
6.80
|
| Locus: PDGFRB/rs919751 Genotype: A/G |
8.20
|
10.00
|
| Locus: PDGFRB/rs919751 Genotype: G/G |
6.40
|
8.20
|
| Locus: PDGFRB/rs2304058 Genotype: G/G |
6.05
|
8.45
|
| Locus: PDGFRB/rs2304058 Genotype: G/C |
8.20
|
7.20
|
| Locus: PDGFRB/rs2304058 Genotype: C/C |
12.05
|
6.20
|
| Locus: PDGFRB/rs1864972 Genotype: G/G |
6.65
|
11.50
|
| Locus: PDGFRB/rs1864972 Genotype: G/A |
8.00
|
6.35
|
| Locus: PDGFRB/rs1864972 Genotype: A/A |
11.30
|
7.90
|
| Locus: PDGFRB/rs3733678 Genotype: G/G |
6.30
|
7.00
|
| Locus: PDGFRB/rs3733678 Genotype: G/A |
14.00
|
5.90
|
| Locus: PDGFRB/rs246396 Genotype: T/T |
8.00
|
5.40
|
| Locus: PDGFRB/rs246396 Genotype: T/C |
7.30
|
14.95
|
| Locus: PDGFRB/rs246396 Genotype: C/C |
NA
|
6.20
|
| Locus: PDGFRB/rs34586048 Genotype: C/C |
8.00
|
6.80
|
| Locus: PDGFRB/rs11740355 Genotype: T/T |
8.20
|
6.20
|
| Locus: PDGFRB/rs11740355 Genotype: T/G |
6.90
|
14.40
|
| Locus: PDGFRB/rs11740355 Genotype: G/G |
1.80
|
NA
|
| Locus: PDGFRB/rs740751 Genotype: C/C |
6.65
|
11.50
|
| Locus: PDGFRB/rs740751 Genotype: C/T |
8.00
|
6.80
|
| Locus: PDGFRB/rs740751 Genotype: T/T |
11.30
|
7.90
|
| Locus: PDGFRB/rs4705415 Genotype: G/G |
11.30
|
6.70
|
| Locus: PDGFRB/rs4705415 Genotype: G/A |
8.20
|
6.80
|
| Locus: PDGFRB/rs4705415 Genotype: A/A |
5.60
|
8.20
|
| Locus: PDGFRB/rs3776075 Genotype: T/T |
6.35
|
14.35
|
| Locus: PDGFRB/rs3776075 Genotype: T/G |
9.30
|
7.20
|
| Locus: PDGFRB/rs3776075 Genotype: G/G |
14.00
|
4.70
|
| Locus: PDGFRB/rs17708574 Genotype: G/G |
9.30
|
6.20
|
| Locus: PDGFRB/rs17708574 Genotype: G/A |
5.40
|
6.80
|
| Locus: PDGFRB/rs10063714 Genotype: T/T |
6.40
|
7.20
|
| Locus: PDGFRB/rs10063714 Genotype: T/A |
14.00
|
5.90
|
| Locus: PDGFRB/rs3776081 Genotype: A/A |
6.30
|
12.95
|
| Locus: PDGFRB/rs3776081 Genotype: A/G |
11.30
|
6.80
|
| Locus: PDGFRB/rs3776081 Genotype: G/G |
11.60
|
4.80
|
| Locus: PDGFRB/rs2007637 Genotype: G/G |
6.90
|
5.40
|
| Locus: PDGFRB/rs2007637 Genotype: G/A |
8.20
|
13.40
|
| Locus: PDGFRB/rs2007637 Genotype: A/A |
8.40
|
NA
|
| Locus: PDGFRB/rs2302273 Genotype: G/G |
7.55
|
11.50
|
| Locus: PDGFRB/rs2302273 Genotype: G/A |
11.30
|
6.20
|
| Locus: PDGFRB/rs2302273 Genotype: A/A |
4.80
|
4.80
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304060 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8563 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.121 | |
| Confidence Interval |
(2-Sided) 95% 0.326 to 3.847 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304060 Genotype: C/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7375 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.111 | |
| Confidence Interval |
(2-Sided) 95% 0.599 to 2.064 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs234060 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8066 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.897 | |
| Confidence Interval |
(2-Sided) 95% 0.375 to 2.147 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17656204 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6945 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.875 | |
| Confidence Interval |
(2-Sided) 95% 0.449 to 1.708 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17656204 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8536 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.067 | |
| Confidence Interval |
(2-Sided) 95% 0.536 to 2.122 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17656204 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3657 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.732 | |
| Confidence Interval |
(2-Sided) 95% 0.283 to 26.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304061 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4657 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.793 | |
| Confidence Interval |
(2-Sided) 95% 0.424 to 1.483 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304061 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4168 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.364 | |
| Confidence Interval |
(2-Sided) 95% 0.641 to 2.900 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1077724 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7836 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.908 | |
| Confidence Interval |
(2-Sided) 95% 0.456 to 1.809 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1077724 Genotype: A/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8531 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.938 | |
| Confidence Interval |
(2-Sided) 95% 0.472 to 1.863 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1077724 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3272 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.320 | |
| Confidence Interval |
(2-Sided) 95% 0.412 to 13.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs919751 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9630 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.984 | |
| Confidence Interval |
(2-Sided) 95% 0.491 to 1.972 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs919751 Genotype: A/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6003 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.227 | |
| Confidence Interval |
(2-Sided) 95% 0.567 to 2.656 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs919751 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6703 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.769 | |
| Confidence Interval |
(2-Sided) 95% 0.229 to 2.580 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304058 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8100 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.106 | |
| Confidence Interval |
(2-Sided) 95% 0.485 to 2.525 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304058 Genotype: G/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8335 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.076 | |
| Confidence Interval |
(2-Sided) 95% 0.541 to 2.141 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2304058 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5980 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.758 | |
| Confidence Interval |
(2-Sided) 95% 0.268 to 2.141 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1864972 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9287 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.035 | |
| Confidence Interval |
(2-Sided) 95% 0.487 to 2.199 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1864972 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8842 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.053 | |
| Confidence Interval |
(2-Sided) 95% 0.526 to 2.106 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs1864972 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8501 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.129 | |
| Confidence Interval |
(2-Sided) 95% 0.316 to 4.028 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3733678 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4118 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.229 | |
| Confidence Interval |
(2-Sided) 95% 0.749 to 2.017 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3733678 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1299 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.286 | |
| Confidence Interval |
(2-Sided) 95% 0.051 to 1.596 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs246396 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1859 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.692 | |
| Confidence Interval |
(2-Sided) 95% 0.399 to 1.200 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs246396 Genotype: T/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0091 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 3.672 | |
| Confidence Interval |
(2-Sided) 95% 1.291 to 10.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs34586048 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8708 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.039 | |
| Confidence Interval |
(2-Sided) 95% 0.654 to 1.652 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs11740355 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9888 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.996 | |
| Confidence Interval |
(2-Sided) 95% 0.590 to 1.681 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs11740355 Genotype: T/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9702 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.020 | |
| Confidence Interval |
(2-Sided) 95% 0.360 to 2.891 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs740751 Genotype: C/C | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9419 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.973 | |
| Confidence Interval |
(2-Sided) 95% 0.466 to 2.032 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs740751 Genotype: C/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7677 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.112 | |
| Confidence Interval |
(2-Sided) 95% 0.549 to 2.252 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs740751 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8501 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.129 | |
| Confidence Interval |
(2-Sided) 95% 0.316 to 4.028 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs4705415 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5233 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.758 | |
| Confidence Interval |
(2-Sided) 95% 0.322 to 1.782 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs4705415 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7500 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.123 | |
| Confidence Interval |
(2-Sided) 95% 0.549 to 2.297 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs4705415 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6614 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.232 | |
| Confidence Interval |
(2-Sided) 95% 0.483 to 3.142 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776075 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2552 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.779 | |
| Confidence Interval |
(2-Sided) 95% 0.652 to 4.855 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776075 Genotype: T/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7931 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.088 | |
| Confidence Interval |
(2-Sided) 95% 0.577 to 2.052 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776075 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1365 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.449 | |
| Confidence Interval |
(2-Sided) 95% 0.152 to 1.331 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 37
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17708574 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5544 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.854 | |
| Confidence Interval |
(2-Sided) 95% 0.504 to 1.447 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 38
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs17708574 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3132 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.721 | |
| Confidence Interval |
(2-Sided) 95% 0.590 to 5.021 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 39
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs10063714 Genotype: T/T | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3698 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.263 | |
| Confidence Interval |
(2-Sided) 95% 0.755 to 2.113 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 40
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs10063714 Genotype: T/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1495 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.411 | |
| Confidence Interval |
(2-Sided) 95% 0.119 to 1.423 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 41
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776081 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1911 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.613 | |
| Confidence Interval |
(2-Sided) 95% 0.781 to 3.332 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 42
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776081 Genotype: A/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5259 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.793 | |
| Confidence Interval |
(2-Sided) 95% 0.384 to 1.636 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 43
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs3776081 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0996 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.331 | |
| Confidence Interval |
(2-Sided) 95% 0.082 to 1.339 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 44
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2007637 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2755 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.752 | |
| Confidence Interval |
(2-Sided) 95% 0.450 to 1.259 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 45
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2007637 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0120 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 4.850 | |
| Confidence Interval |
(2-Sided) 95% 1.253 to 18.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 46
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2302273 Genotype: G/G | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4663 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.274 | |
| Confidence Interval |
(2-Sided) 95% 0.661 to 2.457 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 47
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2302273 Genotype: G/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7097 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.867 | |
| Confidence Interval |
(2-Sided) 95% 0.406 to 1.848 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 48
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Locus: PDGFRB/rs2302273 Genotype: A/A | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5340 |
| Comments | 2-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.607 | |
| Confidence Interval |
(2-Sided) 95% 0.117 to 3.158 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants by Tumor VEGFR Mutation |
|---|---|
| Description | Percentage of participants with VEGFR mutations in DNA from tumor samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis - All Population; data were not analyzed |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | All participants in all phases. |
| Measure Participants | 0 |
| Title | Correlation of Polymorphisms in Stem Cell Factor Receptor (c-Kit), FMS-like Tyrosine Kinase 3 Receptor (FLT-3), and c-FMS With Blood Counts |
|---|---|
| Description | A blood sample (6 mL) was collected before on-study treatment and was used to isolate DNA. These samples were not anonymized. Correlation was investigated by the percentage of participants with anemia (based on hemoglobin count), neutropenia (based on neutrophil count) and thrombocytopenia (based on platelet count) endpoints and genetic variation as measured by c-KIT, FLT-3, and c-FMS was to be analyzed. |
| Time Frame | Baseline (Day 1, Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Blood samples were collected; however, because of the small sample size that resulted in a lack of power for statistical testing, no formal statistical analyses were performed. |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 0 | 0 |
| Title | VEGF-C Ratio to Baseline at Each Timepoint |
|---|---|
| Description | Plasma VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline) |
| Time Frame | Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set; n equals number of participants with evaluable data at specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Cycle 2, Day 1 (n=41, 46) |
0.86
|
1.02
|
| Cycle 3, Day 1 (n=36, 35) |
0.95
|
0.95
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | VEGF-C Ratio to Baseline for Cycle 2, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2702 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | VEGF-C ratio to Baseline for Cycle 3, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7354 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile |
|---|---|
| Description | Includes colony-stimulating factor 1 receptor (CSF-1R), PDGFRalpha, PDGFRbeta, vascular endothelial growth factor (VEGF), VEGF C (VEGF-C), VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), VEGF receptor 3 (VEGFR3), fibroblast growth factor (FGF), FLT-3, KIT (stem cell factor receptor), and RET (rearranged during transfection). Correlative analysis was conducted using tumor biopsy samples collected at the time of initial diagnosis (preferred) or at the time of most recent recurrence/progression, although any time was acceptable. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| CSF-1R/High |
45
346.2%
|
44
258.8%
|
| CSF-1R/Low |
52
400%
|
41
241.2%
|
| CSF-1R/Indeterminate |
3
23.1%
|
15
88.2%
|
| PDGFRalpha/High |
45
346.2%
|
48
282.4%
|
| PDGFRalpha/Low |
52
400%
|
41
241.2%
|
| PDGFRalpha/Indeterminate |
3
23.1%
|
11
64.7%
|
| PDGFRbeta/High |
45
346.2%
|
44
258.8%
|
| PDGFRbeta/Low |
48
369.2%
|
44
258.8%
|
| PDGFRbeta/Indeterminate |
6
46.2%
|
11
64.7%
|
| VEGF/High |
39
300%
|
41
241.2%
|
| VEGF/Low |
39
300%
|
41
241.2%
|
| VEGF/Indeterminate |
23
176.9%
|
19
111.8%
|
| VEGF-C/High |
52
400%
|
41
241.2%
|
| VEGF-C/Low |
45
346.2%
|
52
305.9%
|
| VEGF-C/Indeterminate |
3
23.1%
|
7
41.2%
|
| VEGFR1/High |
35
269.2%
|
44
258.8%
|
| VEGFR1/Low |
48
369.2%
|
33
194.1%
|
| VEGFR1/Indeterminate |
16
123.1%
|
22
129.4%
|
| VEGFR2/High |
45
346.2%
|
48
282.4%
|
| VEGFR2/Low |
52
400%
|
41
241.2%
|
| VEGFR2/Indeterminate |
3
23.1%
|
11
64.7%
|
| VEGFR3/High |
35
269.2%
|
48
282.4%
|
| VEGFR3/Low |
55
423.1%
|
30
176.5%
|
| VEGFR3/Indeterminate |
10
76.9%
|
22
129.4%
|
| FGF/Detected |
10
76.9%
|
19
111.8%
|
| FGF/Not Detected |
84
646.2%
|
67
394.1%
|
| FGF/Indeterminate |
6
46.2%
|
15
88.2%
|
| FLT3/Detected |
26
200%
|
19
111.8%
|
| FLT3/Not Detected |
71
546.2%
|
78
458.8%
|
| FLT3/Indeterminate |
3
23.1%
|
4
23.5%
|
| KIT/Detected |
39
300%
|
30
176.5%
|
| KIT/Not Detected |
58
446.2%
|
67
394.1%
|
| KIT/Indeterminate |
3
23.1%
|
4
23.5%
|
| RET/Detected |
10
76.9%
|
30
176.5%
|
| RET/Not Detected |
84
646.2%
|
59
347.1%
|
| RET/Indeterminate |
6
46.2%
|
11
64.7%
|
| Title | VEGFR-2 Ratio to Baseline at Each Timepoint |
|---|---|
| Description | Plasma VEGFR-2 concentration at each time point divided by VEGFR-2 concentration at baseline (ratio to baseline) |
| Time Frame | Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set; n equals number of participants with evaluable data at specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Cycle 2, Day 1 (n=43, 46) |
0.71
|
0.98
|
| Cycle 3, Day 1 (n=36, 36) |
0.67
|
0.99
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | VEGFR-2 Ratio to Baseline for Cycle 2, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | VEGFR-2 Ratio to Baseline for Cycle 3, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | PFS in Subgroups That Were Defined by RNA Expression Profile |
|---|---|
| Description | PFS, defined as time from date of randomization to date of first documentation of PD or death on-study due to any cause, whichever occurred first, in subgroups that were defined by RNA Gene expression (CSF-1R, PDGFRalpha, PDGFRbeta, VEGF, VEGF-C, VEGFR1, VEGFR2, VEGFR3, FGF, FLT-3, KIT, and RET). PFS was calculated as (first event date minus randomization date plus 1) divided by 7.02. |
| Time Frame | From randomization to Weeks 8 and 12, then every 8 weeks until disease progression or death (up to Month 17) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| CSF-1R/High |
19.1
|
10.9
|
| CSF-1R/Low |
12.3
|
12.3
|
| CSF-1R/Indeterminate |
9.5
|
8.1
|
| PDGFRalpha/High |
12.3
|
52.0
|
| PDGFRalpha/Low |
16.0
|
7.7
|
| PDGFRalpha/Indeterminate |
9.5
|
8.1
|
| PDGFRbeta/High |
12.3
|
11.7
|
| PDGFRbeta/Low |
16.0
|
12.3
|
| PDGFRbeta/Indeterminate |
9.5
|
8.1
|
| VEGF/High |
16.0
|
10.1
|
| VEGF/Low |
19.1
|
11.7
|
| VEGF/Indeterminate |
9.5
|
8.1
|
| VEGF-C/High |
12.3
|
12.1
|
| VEGF-C/Low |
16.0
|
8.5
|
| VEGF-C/Indeterminate |
9.5
|
8.1
|
| VEGFR1/High |
12.5
|
11.2
|
| VEGFR1/Low |
19.1
|
11.7
|
| VEGFR1/Indeterminate |
9.5
|
8.1
|
| VEGFR2/High |
17.0
|
12.3
|
| VEGFR2/Low |
16.0
|
8.8
|
| VEGFR2/Indeterminate |
9.5
|
8.1
|
| VEGFR3/High |
NA
|
12.3
|
| VEGFR3/Low |
12.3
|
8.8
|
| VEGFR3/Indeterminate |
9.5
|
8.0
|
| FGF/Detected |
11.7
|
7.7
|
| FGF/Not Detected |
12.3
|
12.3
|
| FGF/Indeterminate |
9.5
|
8.1
|
| FLT3/Detected |
16.0
|
12.1
|
| FLT3/Not Detected |
17.0
|
8.5
|
| FLT3/Indeterminate |
9.5
|
8.1
|
| KIT/Detected |
19.5
|
10.1
|
| KIT/Not Detected |
16.0
|
11.7
|
| KIT/Indeterminate |
9.5
|
8.1
|
| RET/Detected |
10.4
|
10.1
|
| RET/Not Detected |
12.3
|
11.7
|
| RET/Indeterminate |
9.5
|
8.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High CSF-1R expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1667 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.553 | |
| Confidence Interval |
(2-Sided) 95% 0.159 to 1.921 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low CSF-1R expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7688 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.451 | |
| Confidence Interval |
(2-Sided) 95% 0.534 to 3.944 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate CSF-1R expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3498 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.890 | |
| Confidence Interval |
(2-Sided) 95% 0.503 to 1.574 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High PDGFRalpha expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9497 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.687 | |
| Confidence Interval |
(2-Sided) 95% 0.790 to 9.143 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low PDGFRalpha expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0401 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.386 | |
| Confidence Interval |
(2-Sided) 95% 0.127 to 1.173 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate PDGFRalpha expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3128 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.862 | |
| Confidence Interval |
(2-Sided) 95% 0.487 to 1.524 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High PDGFRbeta expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3650 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.823 | |
| Confidence Interval |
(2-Sided) 95% 0.273 to 2.488 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low PDGFRbeta expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6105 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.192 | |
| Confidence Interval |
(2-Sided) 95% 0.408 to 3.480 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate PDGFRbeta expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3027 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.856 | |
| Confidence Interval |
(2-Sided) 95% 0.488 to 1.502 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High VEGF expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4436 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.914 | |
| Confidence Interval |
(2-Sided) 95% 0.262 to 3.184 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low VEGF expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4582 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.953 | |
| Confidence Interval |
(2-Sided) 95% 0.296 to 3.062 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate VEGF expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3720 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.911 | |
| Confidence Interval |
(2-Sided) 95% 0.536 to 1.548 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High VEGF-C expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5586 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.090 | |
| Confidence Interval |
(2-Sided) 95% 0.350 to 3.397 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low VEGF-C expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3652 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.842 | |
| Confidence Interval |
(2-Sided) 95% 0.313 to 2.266 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate VEGF-C expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3301 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.875 | |
| Confidence Interval |
(2-Sided) 95% 0.493 to 1.554 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High VEGFR1 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5605 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.097 | |
| Confidence Interval |
(2-Sided) 95% 0.331 to 3.636 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low VEGFR1 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2132 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.599 | |
| Confidence Interval |
(2-Sided) 95% 0.160 to 2.236 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate VEGFR1 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3605 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.902 | |
| Confidence Interval |
(2-Sided) 95% 0.530 to 1.537 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High VEGFR2 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4438 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.921 | |
| Confidence Interval |
(2-Sided) 95% 0.304 to 2.784 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low VEGFR2 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5699 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.122 | |
| Confidence Interval |
(2-Sided) 95% 0.403 to 3.125 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate VEGFR2 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3147 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.864 | |
| Confidence Interval |
(2-Sided) 95% 0.489 to 1.528 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | High VEGFR3 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5015 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.002 | |
| Confidence Interval |
(2-Sided) 95% 0.281 to 3.581 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Low VEGFR3 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4887 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.005 | |
| Confidence Interval |
(2-Sided) 95% 0.334 to 3.025 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate VEGFR3 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2432 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.818 | |
| Confidence Interval |
(2-Sided) 95% 0.473 to 1.414 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Detected FGF expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2321 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.446 | |
| Confidence Interval |
(2-Sided) 95% 0.048 to 4.101 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | No detected FGF expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7143 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.316 | |
| Confidence Interval |
(2-Sided) 95% 0.526 to 3.292 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate FGF expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2812 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.844 | |
| Confidence Interval |
(2-Sided) 95% 0.486 to 1.465 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Detected FLT3 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6504 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.406 | |
| Confidence Interval |
(2-Sided) 95% 0.248 to 7.960 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | No detected FLT3 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3266 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.838 | |
| Confidence Interval |
(2-Sided) 95% 0.375 to 1.876 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate FLT3 expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3597 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.896 | |
| Confidence Interval |
(2-Sided) 95% 0.502 to 1.598 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Detected KIT expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6907 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.342 | |
| Confidence Interval |
(2-Sided) 95% 0.419 to 4.297 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Participants with no detected KIT expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1990 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.677 | |
| Confidence Interval |
(2-Sided) 95% 0.265 to 1.731 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate KIT expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3597 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.896 | |
| Confidence Interval |
(2-Sided) 95% 0.502 to 1.598 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Detected RET expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3757 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.693 | |
| Confidence Interval |
(2-Sided) 95% 0.071 to 6.765 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | No detected RET expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3723 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.874 | |
| Confidence Interval |
(2-Sided) 95% 0.358 to 2.130 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | Indeterminate RET expression | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3263 |
| Comments | 1-sided unstratified log-rank test | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.874 | |
| Confidence Interval |
(2-Sided) 95% 0.501 to 1.523 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | VEGFR-3 Ratio to Baseline at Each Timepoint |
|---|---|
| Description | Plasma VEGFR-3 concentration at each time point divided by VEGFR-3 concentration at baseline (ratio to baseline) |
| Time Frame | Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set; n equals number of participants with evaluable data at specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Cycle 2, Day 1 (n=43, 47) |
0.60
|
0.98
|
| Cycle 3, Day 1 (n=36, 36) |
0.57
|
0.92
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | VEGFR-3 Ratio to Baseline for Cycle 2, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | VEGFR-3 Ratio to Baseline for Cycle 3, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | Health Related Quality of Life (HRQoL) and Lung Cancer Related Symptoms as Assessed With European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score |
|---|---|
| Description | EORTC QLQ-C30: self-administered questionnaire assessing global health status/quality of life (QoL), functional domains (physical, role, cognitive, emotional, and social), symptom scales/items (fatigue, pain, nausea and vomiting, dyspnea, insomnia, loss of appetite, constipation, and diarrhea), and financial difficulties. Recall period: past week; response range: not at all (1) to very much (4); global/QoL range: very poor (1) to excellent (7). Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms. |
| Time Frame | Baseline (Cycle [C] 1, Day [D] 1) to Cycle 18, Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patient-Reported Outcome (PRO) Analysis Set: participants from the FA Set who had at least 1 EORTC QLQ-C30 or EORTC QLQ Lung cancer (QLQ-LC13) module questionnaire assessment while on treatment; n is number of participants with an assessment at the specified time point. |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 49 | 54 |
| Global Health Status/QoL (C1, D1) (n=49, 53) |
66.49
|
62.26
|
| Global Health Status/QoL (C2, D1) (n=41, 46) |
62.60
|
57.43
|
| Global Health Status/QoL (C3, D1) (n=27, 32) |
61.73
|
59.12
|
| Global Health Status/QoL (C4, D1) (n=19, 22) |
66.67
|
60.98
|
| Global Health Status/QoL (C5, D1) (n=14, 18) |
69.05
|
61.12
|
| Global Health Status/QoL (C6, D1) (n=8, 14) |
80.20
|
67.27
|
| Global Health Status/QoL (C7, D1) (n=7, 10) |
71.41
|
63.34
|
| Global Health Status/QoL (C8, D1) (n=4, 7) |
89.60
|
59.51
|
| Global Health Status/QoL (C9, D1) (n=4, 5) |
79.18
|
66.66
|
| Global Health Status/QoL (C10, D1) (n=3, 4) |
88.90
|
56.25
|
| Global Health Status/QoL (C11, D1) (n=3, 4) |
86.10
|
62.50
|
| Global Health Status/QoL (C12, D1) (n=3, 4) |
88.90
|
58.33
|
| Global Health Status/QoL (C13, D1) (n=3, 3) |
80.57
|
61.10
|
| Global Health Status/QoL (C14, D1) (n=2, 3) |
75.00
|
55.53
|
| Global Health Status/QoL (C15, D1) (n=1, 2) |
100.00
|
66.65
|
| Global Health Status/QoL (C16, D1) (n=1, 2) |
100.00
|
66.65
|
| Global Health Status/QoL (C17, D1) (n=1, 2) |
100.00
|
58.30
|
| Global Health Status/QoL (C18, D1) (n=1, 2) |
100.00
|
66.65
|
| Physical Functioning (C1, D1) (n=49, 54) |
79.32
|
74.81
|
| Physical Functioning (C2, D1) (n=41, 46) |
77.24
|
72.03
|
| Physical Functioning (C3, D1) (n=28, 32) |
73.58
|
72.28
|
| Physical Functioning (C4, D1) (n=19, 22) |
71.58
|
74.23
|
| Physical Functioning (C5, D1) (n=14, 18) |
75.72
|
68.89
|
| Physical Functioning (C6, D1) (n=9, 14) |
85.92
|
75.24
|
| Physical Functioning (C7, D1) (n=7, 10) |
80.00
|
71.99
|
| Physical Functioning (C8, D1) (n=4, 7) |
93.35
|
74.29
|
| Physical Functioning (C9, D1) (n=4, 5) |
95.00
|
73.32
|
| Physical Functioning (C10, D1) (n=3, 4) |
93.33
|
70.00
|
| Physical Functioning (C11, D1) (n=3, 4) |
93.33
|
71.68
|
| Physical Functioning (C12, D1) (n=3, 4) |
97.77
|
71.68
|
| Physical Functioning (C13, D1) (n=3, 3) |
95.57
|
73.30
|
| Physical Functioning (C14, D1) (n=2, 3) |
93.35
|
68.90
|
| Physical Functioning (C15, D1) (n=1, 2) |
100.00
|
70.00
|
| Physical Functioning (C16, D1) (n=1, 2) |
100.00
|
66.70
|
| Physical Functioning (C17, D1) (n=1, 2) |
100.00
|
70.00
|
| Physical Functioning (C18, D1) (n=1, 2) |
100.00
|
73.30
|
| Role Functioning (C1, D1) (n=49, 53) |
80.95
|
69.18
|
| Role Functioning (C2, D1) (n=41, 46) |
67.89
|
64.13
|
| Role Functioning (C3, D1) (n=28, 32) |
72.63
|
64.07
|
| Role Functioning (C4, D1) (n=19, 22) |
68.43
|
67.43
|
| Role Functioning (C5, D1) (n=14, 17) |
69.06
|
67.65
|
| Role Functioning (C6, D1) (n=9, 14) |
83.34
|
69.05
|
| Role Functioning (C7, D1) (n=7,10) |
85.71
|
73.34
|
| Role Functioning (C8, D1) (n=4, 7) |
91.68
|
69.04
|
| Role Functioning (C9, D1) (n=4, 5) |
91.68
|
66.66
|
| Role Functioning (C10, D1) (n=3, 4) |
94.43
|
50.00
|
| Role Functioning (C11, D1) (n=3, 4) |
94.43
|
62.50
|
| Role Functioning (C12, D1) (n=3, 4) |
100.00
|
62.50
|
| Role Functioning (C13, D1) (n=3, 3) |
88.90
|
72.23
|
| Role Functioning (C14, D1) (n=2, 3) |
83.35
|
66.67
|
| Role Functioning (C15, D1) (n=1, 2) |
100.00
|
83.35
|
| Role Functioning (C16, D1) (n=1, 2) |
100.00
|
66.65
|
| Role Functioning (C17, D1) (n=1, 2) |
100.00
|
58.35
|
| Role Functioning (C18, D1) (n=1, 2) |
100.00
|
66.65
|
| Cognitive Functioning (C1, D1) (n=49, 54) |
85.03
|
82.71
|
| Cognitive Functioning (C2, D1) (n=41, 46) |
86.99
|
82.24
|
| Cognitive Functioning (C3, D1) (n=27, 32) |
87.04
|
82.29
|
| Cognitive Functioning (C4, D1) (n=19, 22) |
89.47
|
81.06
|
| Cognitive Functioning (C5, D1) (n=14, 18) |
82.14
|
81.48
|
| Cognitive Functioning (C6, D1) (n=8, 14) |
85.40
|
84.53
|
| Cognitive Functioning (C7, D1) (n=7, 10) |
85.71
|
89.99
|
| Cognitive Functioning (C8, D1) (n=4, 7) |
91.65
|
71.43
|
| Cognitive Functioning (C9, D1) (n=4, 5) |
91.65
|
83.34
|
| Cognitive Functioning (C10, D1) (n=3, 4) |
94.43
|
79.18
|
| Cognitive Functioning (C11, D1) (n=3, 4) |
94.43
|
87.50
|
| Cognitive Functioning (C12, D1) (n=3, 4) |
94.43
|
79.15
|
| Cognitive Functioning (C13, D1) (n=3, 3) |
94.43
|
83.33
|
| Cognitive Functioning (C14, D1) (n=2, 3) |
100.00
|
83.33
|
| Cognitive Functioning (C15, D1) (n=1, 2) |
100.00
|
100.00
|
| Cognitive Functioning (C16, D1) (n=1, 2) |
100.00
|
91.65
|
| Cognitive Functioning (C17, D1) (n=1, 2) |
100.00
|
83.35
|
| Cognitive Functioning (C18, D1) (n=1, 2) |
100.00
|
100.00
|
| Emotional Functioning (C1, D1) (n=49, 53) |
74.65
|
71.23
|
| Emotional Functioning (C2, D1) (n=41, 46) |
77.85
|
71.37
|
| Emotional Functioning (C3, D1) (n=27, 32) |
76.86
|
67.98
|
| Emotional Functioning (C4, D1) (n=19, 22) |
82.46
|
71.21
|
| Emotional Functioning (C5, D1) (n=14, 18) |
79.18
|
71.30
|
| Emotional Functioning (C6, D1) (n=8, 14) |
78.13
|
79.76
|
| Emotional Functioning (C7, D1) (n=7, 10) |
79.77
|
70.82
|
| Emotional Functioning (C8, D1) (n=4, 7) |
87.50
|
61.90
|
| Emotional Functioning (C9, D1) (n=4, 5) |
91.68
|
78.34
|
| Emotional Functioning (C10, D1) (n=3, 4) |
97.23
|
66.68
|
| Emotional Functioning (C11, D1) (n=3, 4) |
97.23
|
64.60
|
| Emotional Functioning (C12, D1) (n=3, 4) |
94.43
|
54.15
|
| Emotional Functioning (C13, D1) (n=3, 3) |
86.13
|
69.43
|
| Emotional Functioning (C14, D1) (n=2, 3) |
83.35
|
63.90
|
| Emotional Functioning (C15, D1) (n=1, 2) |
91.70
|
75.00
|
| Emotional Functioning (C16, D1) (n=1, 2) |
91.70
|
75.00
|
| Emotional Functioning (C17, D1) (n=1, 2) |
100.00
|
62.50
|
| Emotional Functioning (C18, D1) (n=1, 2) |
100.00
|
83.35
|
| Social Functioning (C1, D1) (n=49, 53) |
80.95
|
80.19
|
| Social Functioning (C2, D1) (n=41, 46) |
80.09
|
77.53
|
| Social Functioning (C3, D1) (n=27, 32) |
79.01
|
81.26
|
| Social Functioning (C4, D1) (n=19, 22) |
81.58
|
75.75
|
| Social Functioning (C5, D1) (n=14, 18) |
76.19
|
75.93
|
| Social Functioning (C6, D1) (n=8, 14) |
89.58
|
80.96
|
| Social Functioning (C7, D1) (n=7, 10) |
90.47
|
85.00
|
| Social Functioning (C8, D1) (n=4, 7) |
91.68
|
73.81
|
| Social Functioning (C9, D1) (n=4, 5) |
91.68
|
83.34
|
| Social Functioning (C10, D1) (n=3, 4) |
88.90
|
83.33
|
| Social Functioning (C11, D1) (n=3, 4) |
94.43
|
62.50
|
| Social Functioning (C12, D1) (n=3, 4) |
94.43
|
66.68
|
| Social Functioning (C13, D1) (n=3, 3) |
88.90
|
72.23
|
| Social Functioning (C14, D1) (n=2, 3) |
83.35
|
72.20
|
| Social Functioning (C15, D1) (n=1, 2) |
100.00
|
91.65
|
| Social Functioning (C16, D1) (n=1, 2) |
100.00
|
91.65
|
| Social Functioning (C17, D1) (n=1, 2) |
100.00
|
83.35
|
| Social Functioning (C18, D1) (n=1, 2) |
100.00
|
91.65
|
| Fatigue (C1, D1) (n=49, 53) |
32.64
|
33.11
|
| Fatigue (C2, D1) (n=41, 46) |
37.93
|
39.85
|
| Fatigue (C3, D1) (n=28, 32) |
40.07
|
37.49
|
| Fatigue (C4, D1) (n=19, 22) |
36.25
|
33.84
|
| Fatigue (C5, D1) (n=14, 18) |
31.73
|
44.44
|
| Fatigue (C6, D1) (n=9, 14) |
21.59
|
33.32
|
| Fatigue (C7, D1) (n=7, 10) |
25.40
|
33.32
|
| Fatigue (C8, D1) (n=4, 7) |
8.33
|
39.69
|
| Fatigue (C9, D1) (n=4, 5) |
13.88
|
28.90
|
| Fatigue (C10, D1) (n=3, 4) |
7.40
|
36.10
|
| Fatigue (C11, D1) (n=3, 4) |
25.90
|
30.55
|
| Fatigue (C12, D1) (n=3, 4) |
14.80
|
27.78
|
| Fatigue (C13, D1) (n=3, 3) |
11.10
|
25.90
|
| Fatigue (C14, D1) (n=2, 3) |
16.65
|
40.73
|
| Fatigue (C15, D1) (n=1, 2) |
NA
|
16.65
|
| Fatigue (C16, D1) (n=1, 2) |
NA
|
38.90
|
| Fatigue (C17, D1) (n=1, 2) |
NA
|
33.35
|
| Fatigue (C18, D1) (n=1, 2) |
NA
|
33.35
|
| Nausea/Vomiting (C1, D1) (n=49, 54) |
7.49
|
9.26
|
| Nausea/Vomiting (C2, D1) (n=41, 46) |
16.26
|
14.13
|
| Nausea/Vomiting (C3, D1) (n=28, 32) |
16.67
|
11.98
|
| Nausea/Vomiting (C4, D1) (n=19, 22) |
13.16
|
6.82
|
| Nausea/Vomiting (C5, D1) (n=14, 18) |
16.66
|
8.34
|
| Nausea/Vomiting (C6, D1) (n=9, 14) |
9.26
|
2.39
|
| Nausea/Vomiting (C7, D1) (n=7, 10) |
16.67
|
8.34
|
| Nausea/Vomiting (C8, D1) (n=4, 7) |
NA
|
9.51
|
| Nausea/Vomiting (C9, D1) (n=4, 5) |
4.18
|
6.66
|
| Nausea/Vomiting (C10, D1) (n=3, 4) |
11.10
|
12.50
|
| Nausea/Vomiting (C11, D1) (n=3, 4) |
16.67
|
8.35
|
| Nausea/Vomiting (C12, D1) (n=3, 4) |
5.57
|
NA
|
| Nausea/Vomiting (C17, D1) (n=1, 2) |
NA
|
8.35
|
| Pain (C1, D1) (n=49, 54) |
25.85
|
30.25
|
| Pain (C2, D1) (n=41, 46) |
19.51
|
31.52
|
| Pain (C3, D1) (n=28, 32) |
19.05
|
28.65
|
| Pain (C4, D1) (n=19, 22) |
16.67
|
28.80
|
| Pain (C5, D1) (n=14, 18) |
21.43
|
33.34
|
| Pain (C6, D1) (n=9, 14) |
12.98
|
25.00
|
| Pain (C7, D1) (n=7, 10) |
19.06
|
23.34
|
| Pain (C8, D1) (n=4, 7) |
12.5
|
19.04
|
| Pain (C9, D1) (n=4, 5) |
8.33
|
20.00
|
| Pain (C10, D1) (n=3, 4) |
NA
|
16.65
|
| Pain (C11, D1) (n=3, 4) |
NA
|
24.98
|
| Pain (C12, D1) (n=3, 4) |
NA
|
24.98
|
| Pain (C13, D1) (n=3, 3) |
11.10
|
22.20
|
| Pain (C14, D1) (n=2, 3) |
16.65
|
22.20
|
| Pain (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Pain (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Pain (C18, D1) (n=1, 2) |
NA
|
16.65
|
| Dyspnea (C1, D1) (n=49, 54) |
26.51
|
25.91
|
| Dyspnea (C2, D1) (n=41, 46) |
30.07
|
26.80
|
| Dyspnea (C3, D1) (n=28, 32) |
26.18
|
24.99
|
| Dyspnea (C4, D1) (n=19, 22) |
36.83
|
25.75
|
| Dyspnea (C5, D1) (n=14, 18) |
30.94
|
29.62
|
| Dyspnea (C6, D1) (n=9, 14) |
25.91
|
23.79
|
| Dyspnea (C7, D1) (n=7, 10) |
33.33
|
19.98
|
| Dyspnea (C8, D1) (n=4, 7) |
16.65
|
23.81
|
| Dyspnea (C9, D1) (n=4, 5) |
16.65
|
6.66
|
| Dyspnea (C10, D1) (n=3, 4) |
22.23
|
16.68
|
| Dyspnea (C11, D1) (n=3, 4) |
33.33
|
8.33
|
| Dyspnea (C12, D1) (n=3, 4) |
22.23
|
8.33
|
| Dyspnea (C13, D1) (n=3, 3) |
11.10
|
22.20
|
| Dyspnea (C14, D1) (n=2, 3) |
16.65
|
22.20
|
| Dyspnea (C15, D1) (n=1, 2) |
33.30
|
16.65
|
| Dyspnea (C16, D1) (n=1, 2) |
NA
|
33.30
|
| Dyspnea (C17, D1) (n=1, 2) |
NA
|
33.35
|
| Dyspnea (C18, D1) (n=1, 2) |
NA
|
16.65
|
| Insomnia (C1, D1) (n=49, 54) |
29.24
|
27.78
|
| Insomnia (C2, D1) (n=41, 46) |
22.76
|
29.71
|
| Insomnia (C3, D1) (n=28, 32) |
29.75
|
38.54
|
| Insomnia (C4, D1) (n=19, 22) |
14.03
|
25.76
|
| Insomnia (C5, D1) (n=14, 18) |
19.04
|
33.33
|
| Insomnia (C6, D1) (n=9, 14) |
11.10
|
23.81
|
| Insomnia (C7, D1) (n=7, 10) |
14.29
|
19.99
|
| Insomnia (C8, D1) (n=4, 7) |
33.33
|
38.09
|
| Insomnia (C9, D1) (n=4, 5) |
24.98
|
33.32
|
| Insomnia (C10, D1) (n=3, 4) |
22.23
|
41.68
|
| Insomnia (C11, D1) (n=3, 4) |
33.33
|
33.33
|
| Insomnia (C12, D1) (n=3, 4) |
33.33
|
16.65
|
| Insomnia (C13, D1) (n=3, 3) |
22.20
|
22.20
|
| Insomnia (C14, D1) (n=2, 3) |
33.30
|
44.47
|
| Insomnia (C15, D1) (n=1, 2) |
33.30
|
16.65
|
| Insomnia (C16, D1) (n=1, 2) |
33.30
|
16.65
|
| Insomnia (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Insomnia (C18, D1) (n=1, 2) |
NA
|
16.65
|
| Loss of Appetite (C1, D1) (n=49, 54) |
23.12
|
20.99
|
| Loss of Appetite (C2, D1) (n=41, 46) |
33.33
|
26.81
|
| Loss of Appetite (C3, D1) (n=28, 32) |
36.90
|
26.04
|
| Loss of Appetite (C4, D1) (n=19, 22) |
28.06
|
24.24
|
| Loss of Appetite (C5, D1) (n=14, 18) |
26.18
|
24.08
|
| Loss of Appetite (C6, D1) (n=9, 14) |
22.21
|
26.19
|
| Loss of Appetite (C7, D1) (n=7, 10) |
28.56
|
30.00
|
| Loss of Appetite (C8, D1) (n=4, 7) |
16.65
|
14.29
|
| Loss of Appetite (C9, D1) (n=4, 5) |
16.65
|
20.00
|
| Loss of Appetite (C10, D1) (n=3, 4) |
22.23
|
25.00
|
| Loss of Appetite (C11, D1) (n=3, 4) |
22.23
|
33.33
|
| Loss of Appetite (C12, D1) (n=3, 4) |
22.20
|
25.00
|
| Loss of Appetite (C13, D1) (n=3, 3) |
22.20
|
11.10
|
| Loss of Appetite (C14, D1) (n=2, 3) |
16.65
|
11.10
|
| Loss of Appetite (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Constipation (C1, D1) (n=48, 54) |
12.49
|
16.67
|
| Constipation (C2, D1) (n=41, 46) |
4.88
|
13.77
|
| Constipation (C3, D1) (n=28, 32) |
13.10
|
18.75
|
| Constipation (C4, D1) (n=19, 22) |
1.75
|
10.60
|
| Constipation (C5, D1) (n=14, 18) |
7.14
|
14.82
|
| Constipation (C6, D1) (n=8, 13) |
12.50
|
12.82
|
| Constipation (C7, D1) (n=7, 10) |
4.76
|
3.33
|
| Constipation (C8, D1) (n=4, 7) |
8.33
|
NA
|
| Constipation (C9, D1) (n=4, 5) |
8.33
|
13.34
|
| Constipation (C10, D1) (n=3, 4) |
NA
|
8.33
|
| Constipation (C11, D1) (n=3, 4) |
NA
|
8.33
|
| Constipation (C12, D1) (n=3, 4) |
11.10
|
8.33
|
| Constipation (C13, D1) (n=3, 3) |
11.10
|
NA
|
| Constipation (C14, D1) (n=2, 3) |
16.65
|
NA
|
| Constipation (C15, D1) (n=1, 2) |
NA
|
16.65
|
| Diarrhea (C1, D1) (n=49, 54) |
6.80
|
2.47
|
| Diarrhea (C2, D1) (n=41, 46) |
38.21
|
21.01
|
| Diarrhea (C3, D1) (n=27, 32) |
37.03
|
17.69
|
| Diarrhea (C4, D1) (n=19, 22) |
38.59
|
7.57
|
| Diarrhea (C5, D1) (n=14, 18) |
30.94
|
14.81
|
| Diarrhea (C6, D1) (n=8, 14) |
24.99
|
11.90
|
| Diarrhea (C7, D1) (n=7, 10) |
42.86
|
6.66
|
| Diarrhea (C8, D1) (n=4, 7) |
33.30
|
14.29
|
| Diarrhea (C9, D1) (n=4, 5) |
33.30
|
6.66
|
| Diarrhea (C10, D1) (n=3, 4) |
33.33
|
8.33
|
| Diarrhea (C11, D1) (n=3, 4) |
33.33
|
16.65
|
| Diarrhea (C12, D1) (n=3, 4) |
66.67
|
16.65
|
| Diarrhea (C13, D1) (n=3, 3) |
33.30
|
11.10
|
| Diarrhea (C14, D1) (n=2, 3) |
50.00
|
11.10
|
| Diarrhea (C15, D1) (n=1, 2) |
NA
|
16.65
|
| Diarrhea (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Diarrhea (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Diarrhea (C18, D1) (n=1, 2) |
NA
|
16.65
|
| Financial Difficulties (C1, D1) (n=49, 53) |
21.76
|
13.84
|
| Financial Difficulties (C2, D1) (n=41, 45) |
17.07
|
11.85
|
| Financial Difficulties (C3, D1) (n=27, 32) |
17.27
|
16.66
|
| Financial Difficulties (C4, D1) (n=19, 22) |
8.77
|
24.25
|
| Financial Difficulties (C5, D1) (n=14, 18) |
21.42
|
16.67
|
| Financial Difficulties (C6, D1) (n=8, 14) |
24.99
|
19.05
|
| Financial Difficulties (C7, D1) (n=7, 10) |
9.51
|
13.33
|
| Financial Difficulties (C8, D1) (n=4, 7) |
41.65
|
38.10
|
| Financial Difficulties (C9, D1) (n=4, 5) |
33.33
|
26.66
|
| Financial Difficulties (C10, D1) (n=3, 4) |
44.43
|
33.33
|
| Financial Difficulties (C11, D1) (n=3, 4) |
44.43
|
33.33
|
| Financial Difficulties (C12, D1) (n=3, 4) |
44.43
|
33.33
|
| Financial Difficulties (C13, D1) (n=3, 3) |
44.43
|
33.33
|
| Financial Difficulties (C14, D1) (n=2, 3) |
66.65
|
33.33
|
| Financial Difficulties (C15, D1) (n=1, 2) |
100.00
|
NA
|
| Financial Difficulties (C16, D1) (n=1, 2) |
100
|
NA
|
| Title | sKIT Ratio to Baseline at Each Timepoint |
|---|---|
| Description | Plasma sKIT concentration at each time point divided by sKIT concentration at baseline (ratio to baseline) |
| Time Frame | Baseline to Cycle 2 (Day 1) and Cycle 3 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set; n equals number of participants with evaluable data at specified cycle |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Cycle 2, Day 1 (n=43, 47) |
0.76
|
1.00
|
| Cycle 3, Day 1 (n=36, 36) |
0.58
|
0.95
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | sKIT Ratio to Baseline for Cycle 2, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | sKIT Ratio to Baseline for Cycle 3, Day 1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | EORTC-QLQ-C30 Lung Cancer Module (LC13) Score |
|---|---|
| Description | The EORTC-QLQ-C30 LC13 is a self-administered questionnaire assessing specific lung cancer disease related symptoms (dyspnea, coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in the chest, arm/shoulder or other parts of the body). Recall period: past week; response range: not at all (1) to very much (4). Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. |
| Time Frame | Baseline (Cycle 1 [Day 1]) to Cycle 18 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PRO Analysis Set; n is number of participants with an assessment at the specific time point |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 49 | 54 |
| Dyspnea Symptom (C1, D1) (n=48, 53) |
21.05
|
25.56
|
| Dyspnea Symptom (C2, D1) (n=38, 46) |
25.71
|
26.08
|
| Dyspnea Symptom (C3, D1) (n=26, 32) |
24.77
|
26.03
|
| Dyspnea Symptom (C4, D1) (n=18, 22) |
27.16
|
23.73
|
| Dyspnea Symptom (C5, D1) (n=12, 18) |
22.21
|
32.71
|
| Dyspnea Symptom (C6, D1) (n=8, 14) |
18.04
|
21.41
|
| Dyspnea Symptom (C7, D1) (n=6, 10) |
14.80
|
29.99
|
| Dyspnea Symptom (C8, D1) (n=4, 6) |
8.33
|
22.22
|
| Dyspnea Symptom (C9, D1) (n=4, 3) |
11.10
|
22.20
|
| Dyspnea Symptom (C10, D1) (n=3, 4) |
11.10
|
33.33
|
| Dyspnea Symptom (C11, D1) (n=3, 3) |
18.50
|
29.60
|
| Dyspnea Symptom (C12, D1) (n=3, 4) |
14.80
|
22.20
|
| Dyspnea Symptom (C13, D1) (n=3, 3) |
7.40
|
22.20
|
| Dyspnea Symptom (C14, D1) (n=2, 3) |
16.65
|
25.90
|
| Dyspnea Symptom (C15, D1) (n=1, 2) |
22.20
|
11.10
|
| Dyspnea Symptom (C16, D1) (n=1, 2) |
NA
|
22.20
|
| Dyspnea Symptom (C17, D1) (n=1, 2) |
NA
|
22.20
|
| Dyspnea Symptom (C18, D1) (n=1, 2) |
NA
|
16.65
|
| Coughing Symptom (C1, D1) (n=49, 53) |
36.72
|
37.10
|
| Coughing Symptom (C2, D1) (n=41, 46) |
31.70
|
31.87
|
| Coughing Symptom (C3, D1) (n=27, 32) |
32.09
|
30.20
|
| Coughing Symptom (C4, D1) (n=19, 22) |
29.81
|
15.14
|
| Coughing Symptom (C5, D1) (n=14, 18) |
38.08
|
29.62
|
| Coughing Symptom (C6, D1) (n=9, 14) |
33.31
|
26.17
|
| Coughing Symptom (C7, D1) (n=7, 10) |
33.33
|
16.67
|
| Coughing Symptom (C8, D1) (n=4, 7) |
24.98
|
28.56
|
| Coughing Symptom (C9, D1) (n=4, 4) |
24.98
|
8.33
|
| Coughing Symptom (C10, D1) (n=3, 4) |
22.20
|
25.00
|
| Coughing Symptom (C11, D1) (n=3, 3) |
22.20
|
33.33
|
| Coughing Symptom (C12, D1) (n=3, 4) |
22.20
|
41.65
|
| Coughing Symptom (C13, D1) (n=3, 3) |
22.20
|
33.33
|
| Coughing Symptom (C14, D1) (n=2, 3) |
16.65
|
11.10
|
| Coughing Symptom (C15, D1) (n=1, 2) |
NA
|
16.65
|
| Coughing Symptom (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Coughing Symptom (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Coughing Symptom (C18, D1) (n=1, 2) |
NA
|
33.35
|
| Haemoptysis Symptom (C1, D1) (n=49, 54) |
2.04
|
6.17
|
| Haemoptysis Symptom (C2, D1) (n=41, 46) |
6.50
|
4.34
|
| Haemoptysis Symptom (C3, D1) (n=27, 32) |
2.47
|
5.21
|
| Haemoptysis Symptom (C4, D1) (n=19, 22) |
1.75
|
1.51
|
| Haemoptysis Symptom (C5, D1) (n=14, 18) |
2.38
|
5.56
|
| Haemoptysis Symptom (C6, D1) (n=9, 14) |
3.70
|
2.38
|
| Haemoptysis Symptom (C7, D1) (n=7, 10) |
4.76
|
NA
|
| Haemoptysis Symptom (C8, D1) (n=4, 6) |
NA
|
5.55
|
| Sore Mouth Symptom (C1, D1) (n=49, 54) |
6.12
|
1.23
|
| Sore Mouth Symptom (C2, D1) (n=41, 46) |
19.50
|
7.97
|
| Sore Mouth Symptom (C3, D1) (n=27, 32) |
16.04
|
6.25
|
| Sore Mouth Symptom (C4, D1) (n=19, 22) |
12.27
|
7.58
|
| Sore Mouth Symptom (C5, D1) (n=14, 18) |
23.79
|
12.96
|
| Sore Mouth Symptom (C6, D1) (n=9, 14) |
11.10
|
2.38
|
| Sore Mouth Symptom (C7, D1) (n=7, 10) |
4.76
|
6.67
|
| Sore Mouth Symptom (C8, D1) (n=4, 6) |
NA
|
5.55
|
| Sore Mouth Symptom (C10, D1) (n=3, 4) |
NA
|
8.33
|
| Sore Mouth Symptom (C13, D1) (n=3, 3) |
NA
|
11.10
|
| Sore Mouth Symptom (C14, D1) (n=2, 3) |
NA
|
11.10
|
| Dysphagia Symptom (C1, D1) (n=49, 54) |
6.80
|
6.17
|
| Dysphagia Symptom (C2, D1) (n=41, 46) |
13.00
|
10.14
|
| Dysphagia Symptom (C3, D1) (n=26, 32) |
7.68
|
14.58
|
| Dysphagia Symptom (C4, D1) (n=19, 22) |
7.01
|
12.12
|
| Dysphagia Symptom (C5, D1) (n=14, 18) |
11.91
|
11.11
|
| Dysphagia Symptom (C6, D1) (n=9, 14) |
3.70
|
7.14
|
| Dysphagia Symptom (C7, D1) (n=7, 10) |
4.76
|
10.00
|
| Dysphagia Symptom (C8, D1) (n=4, 6) |
8.33
|
NA
|
| Dysphagia Symptom (C9, D1) (n=4, 3) |
8.33
|
NA
|
| Dysphagia Symptom (C10, D1) (n=3, 4) |
22.23
|
16.65
|
| Dysphagia Symptom (C11, D1) (n=3, 3) |
11.10
|
NA
|
| Dysphagia Symptom (C12, D1) (n=3, 4) |
22.23
|
8.33
|
| Dysphagia Symptom (C13, D1) (n=3, 3) |
NA
|
22.20
|
| Dysphagia Symptom (C14, D1) (n=2, 3) |
NA
|
11.10
|
| Peripheral Neuropathy Symptom (C1, D1) (n=49, 54) |
18.37
|
17.28
|
| Peripheral Neuropathy Symptom (C2, D1) (n=41, 46) |
14.63
|
20.28
|
| Peripheral Neuropathy Symptom (C3, D1) (n=27, 32) |
16.04
|
34.37
|
| Peripheral Neuropathy Symptom (C4, D1) (n=19, 22) |
22.81
|
25.75
|
| Peripheral Neuropathy Symptom (C5, D1) (n=14, 18) |
26.18
|
22.22
|
| Peripheral Neuropathy Symptom (C6, D1) (n=9, 14) |
18.51
|
23.81
|
| Peripheral Neuropathy Symptom (C7, D1) (n=7, 10) |
33.33
|
23.33
|
| Peripheral Neuropathy Symptom (C8, D1) (n=4, 6) |
24.98
|
22.20
|
| Peripheral Neuropathy Symptom (C9, D1) (n=4, 3) |
16.65
|
33.30
|
| Peripheral Neuropathy Symptom (C10, D1) (n=3, 4) |
NA
|
33.30
|
| Peripheral Neuropathy Symptom (C11, D1) (n=3, 3) |
22.20
|
44.43
|
| Peripheral Neuropathy Symptom (C12, D1) (n=3, 4) |
22.23
|
41.65
|
| Peripheral Neuropathy Symptom (C13, D1) (n=3, 3) |
11.10
|
44.43
|
| Peripheral Neuropathy Symptom (C14, D1) (n=2, 3) |
16.65
|
44.43
|
| Peripheral Neuropathy Symptom (C15, D1) (n=1, 2) |
NA
|
16.65
|
| Peripheral Neuropathy Symptom (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Peripheral Neuropathy Symptom (C17, D1) (n=1, 2) |
NA
|
33.30
|
| Peripheral Neuropathy Symptom (C18, D1) (n=1, 2) |
NA
|
33.30
|
| Alopecia Symptom (C1, D1) (n=49, 54) |
12.92
|
12.96
|
| Alopecia Symptom (C2, D1) (n=41, 46) |
4.87
|
5.79
|
| Alopecia Symptom (C3, D1) (n=27, 32) |
7.40
|
5.20
|
| Alopecia Symptom (C4, D1) (n=19, 22) |
10.52
|
13.63
|
| Alopecia Symptom (C5, D1) (n=14, 18) |
16.66
|
22.22
|
| Alopecia Symptom (C6, D1) (n=9, 14) |
14.80
|
19.04
|
| Alopecia Symptom (C7, D1) (n=7, 10) |
14.27
|
16.67
|
| Alopecia Symptom (C8, D1) (n=4, 6) |
8.33
|
11.10
|
| Alopecia Symptom (C9, D1) (n=4, 3) |
16.65
|
22.23
|
| Alopecia Symptom (C10, D1) (n=3, 4) |
11.10
|
25.00
|
| Alopecia Symptom (C11, D1) (n=3, 3) |
33.30
|
NA
|
| Alopecia Symptom (C12, D1) (n=3, 4) |
33.33
|
25.00
|
| Alopecia Symptom (C13, D1) (n=3, 3) |
33.30
|
33.33
|
| Alopecia Symptom (C14, D1) (n=2, 3) |
33.35
|
33.33
|
| Pain in Chest Symptom (C1, D1) (n=49, 53) |
19.72
|
15.09
|
| Pain in Chest Symptom (C2, D1) (n=41, 46) |
11.38
|
14.48
|
| Pain in Chest Symptom (C3, D1) (n=27, 32) |
8.64
|
18.75
|
| Pain in Chest Symptom (C4, D1) (n=18, 22) |
11.11
|
10.60
|
| Pain in Chest Symptom (C5, D1) (n=14, 18) |
16.66
|
20.37
|
| Pain in Chest Symptom (C6, D1) (n=9, 14) |
11.10
|
11.90
|
| Pain in Chest Symptom (C7, D1) (n=7, 10) |
19.03
|
16.66
|
| Pain in Chest Symptom (C8, D1) (n=4, 6) |
8.33
|
5.55
|
| Pain in Chest Symptom (C9, D1) (n=4, 3) |
8.33
|
NA
|
| Pain in Chest Symptom (C10, D1) (n=3, 4) |
NA
|
16.65
|
| Pain in Chest Symptom (C11, D1) (n=3, 3) |
NA
|
11.10
|
| Pain in Chest Symptom (C12, D1) (n=3, 4) |
NA
|
8.33
|
| Pain in Chest Symptom (C13, D1) (n=3, 3) |
11.10
|
22.20
|
| Pain in Chest Symptom (C14, D1) (n=2, 3) |
16.65
|
11.10
|
| Pain in Chest Symptom (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Pain in Chest Symptom (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Pain in Arm or Shoulder (C1, D1) (n=49, 54) |
21.08
|
11.72
|
| Pain in Arm or Shoulder (C2, D1) (n=41, 46) |
10.56
|
16.66
|
| Pain in Arm or Shoulder (C3, D1) (n=27, 32) |
14.81
|
17.71
|
| Pain in Arm or Shoulder (C4, D1) (n=19, 22) |
12.27
|
21.21
|
| Pain in Arm or Shoulder (C5, D1) (n=14, 18) |
19.04
|
25.92
|
| Pain in Arm or Shoulder (C6, D1) (n=9, 14) |
14.80
|
26.19
|
| Pain in Arm or Shoulder (C7, D1) (n=7, 10) |
23.80
|
23.33
|
| Pain in Arm or Shoulder (C8, D1) (n=4, 6) |
16.65
|
5.55
|
| Pain in Arm or Shoulder (C9, D1) (n=4, 3) |
16.65
|
11.10
|
| Pain in Arm or Shoulder (C10, D1) (n=3, 4) |
11.10
|
8.33
|
| Pain in Arm or Shoulder (C11, D1) (n=3, 3) |
11.10
|
11.10
|
| Pain in Arm or Shoulder (C12, D1) (n=3, 4) |
11.10
|
8.33
|
| Pain in Arm or Shoulder (C13, D1) (n=3, 3) |
22.20
|
22.20
|
| Pain in Arm or Shoulder (C14, D1) (n=2, 3) |
16.65
|
11.10
|
| Pain in Arm or Shoulder (C15, D1) (n=1, 2) |
NA
|
16.65
|
| Pain in Arm or Shoulder (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Pain in Arm or Shoulder (C17, D1) (n=1, 2) |
NA
|
16.65
|
| Pain in Arm or Shoulder (C18, D1) (n=1, 2) |
NA
|
16.65
|
| Pain in Other Parts of Body (C1, D1) (n=48, 51) |
26.38
|
35.29
|
| Pain in Other Parts of Body (C2, D1) (n=40, 43) |
14.17
|
28.68
|
| Pain in Other Parts of Body (C3, D1) (n=26, 31) |
16.67
|
29.03
|
| Pain in Other Parts of Body (C4, D1) (n=18, 20) |
14.81
|
20.00
|
| Pain in Other Parts of Body (C5, D1) (n=13, 18) |
35.90
|
31.48
|
| Pain in Other Parts of Body (C6, D1) (n=9, 14) |
18.51
|
21.43
|
| Pain in Other Parts of Body (C7, D1) (n=6, 10) |
16.67
|
33.34
|
| Pain in Other Parts of Body (C8, D1) (n=4, 6) |
NA
|
27.77
|
| Pain in Other Parts of Body (C9, D1) (n=4, 3) |
NA
|
22.20
|
| Pain in Other Parts of Body (C10, D1) (n=3, 4) |
NA
|
8.33
|
| Pain in Other Parts of Body (C11, D1) (n=3, 3) |
NA
|
11.10
|
| Pain in Other Parts of Body (C12, D1) (n=3, 4) |
NA
|
8.33
|
| Pain in Other Parts of Body (C13, D1) (n=3, 3) |
NA
|
22.20
|
| Pain in Other Parts of Body (C14, D1) (n=2, 3) |
16.65
|
NA
|
| Pain in Other Parts of Body (C16, D1) (n=1, 2) |
NA
|
16.65
|
| Title | Number of Participants With Blood Pressure (BP) Greater Than 150/100 Millimeters of Mercury (mmHg) |
|---|---|
| Description | Systolic/diastolic BP measured in triplicate (separated by approximately 2 minutes [min]) using validated electronic device (same device for all measurements), recorded to nearest mmHg. Dominant arm used (same one each time) with appropriate cuff size encircling at least 80% of arm. BP measured after 5 min rest and before invasive procedures, while seated in a chair with back supported, arms bared, supported at heart level. No smoking or caffeine use allowed during 30 min before measurement. Number of participants with systolic BP >150 mmHg/diastolic BP >100 mmHg at any timepoint postbaseline. |
| Time Frame | Randomization up until Month 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-Protocol Set: all participants in the Phase 2 portion (randomized) who received at least 1 dose of study medication (either erlotinib or blinded medication) with treatment assignments designated according to actual study medication received |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 64 | 64 |
| Number [Participants] |
10
76.9%
|
8
47.1%
|
| Title | Number of Participants With BP Greater Than 200/110 mmHg |
|---|---|
| Description | Systolic/diastolic BP measured in triplicate (separated by approximately 2 minutes [min]) using validated electronic device (same device for all measurements), recorded to nearest mmHg. Dominant arm used (same one each time) with appropriate cuff size encircling at least 80% of arm. BP measured after 5 min rest and before invasive procedures, while seated in a chair with back supported, arms bared, supported at heart level. No smoking or caffeine use allowed during 30 min before measurement. Number of participants with systolic BP >150 mmHg/diastolic BP >100 mmHg at any timepoint postbaseline. |
| Time Frame | Randomization up until Month 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per-Protocol Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 64 | 64 |
| Number [Participants] |
1
7.7%
|
0
0%
|
| Title | Number of Participants on Anti-hypertensive Medications |
|---|---|
| Description | Number of participants with BP greater than 150/100 mmHg or 200/110 mmHg who were treated with anti-hypertensive medications. |
| Time Frame | Randomization to Day 28 of Cycle 18 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per Protocol Set; data were not analyzed |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 0 | 0 |
| Title | Plasma Concentration of VEGF-C at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline (Cycle 1, Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (Full Range) [picograms (pg)/mL] |
474.15
|
502.10
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3681 |
| Comments | 2-sided normal approximated p-value | |
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | Plasma Concentration of Soluble VEGFR-2 at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline (Cycle 1, Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (Full Range) [pg/mL] |
10904.50
|
10027
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5982 |
| Comments | 2-sided normal approximated p-value | |
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | Plasma Concentration of Soluble VEGFR-3 at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline (Cycle 1, Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (Full Range) [pg/mL] |
23190
|
23350
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9807 |
| Comments | 2-sided normal approximated p-value | |
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
| Title | Plasma Concentration of Soluble KIT (sKIT) at Baseline |
|---|---|
| Description | |
| Time Frame | Baseline (Cycle 1, Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FA Set |
| Arm/Group Title | Sunitinib + Erlotinib | Erlotinib + Placebo |
|---|---|---|
| Arm/Group Description | Erlotinib 150 mg oral tablets once daily (QD) in a continuous regimen expressed in 4-week cycles and Sunitinib 37.5 mg oral capsules QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. |
| Measure Participants | 65 | 67 |
| Median (Full Range) [pg/mL] |
49520
|
47242.50
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Sunitinib + Erlotinib, Erlotinib + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3945 |
| Comments | 2-sided normal approximated p-value | |
| Method | Wilcoxon Rank Sum Test | |
| Comments | ||
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Total number (#) of participants affected/at risk = number of participants with data for summary/number of participants who received at least 1 dose of study treatment | |||||||
| Arm/Group Title | Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-in) | Sunitinib + Erlotinib | Erlotinib + Placebo | ||||
| Arm/Group Description | Sunitinib 37.5 mg oral capsules once daily (QD) for 28 days each cycle with exception of Cycle 2 (27 days) and Erlotinib 150 mg oral tablets QD for 28 days each cycle with exception of Cycle 1 (35 days). | Sunitinib 37.5 mg oral capsules QD for 28 days each cycle (27 days in Cycle 1, Arm A or 13 days in Cycle 1, Arm B) and Erlotinib 150 mg oral tablets QD for 28 days each cycle (7 days in Cycle 1, Arm A or 26 days in Cycle 1, Arm B) | Sunitinib oral capsules, 37.5 mg QD in a continuous regimen, expressed in 4-week cycles and Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles. | Erlotinib 150 mg oral tablets QD in a continuous regimen expressed in 4-week cycles and Placebo oral capsules QD in a continuous regimen expressed in 4-week cycles. | ||||
All Cause Mortality |
||||||||
| Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-in) | Sunitinib + Erlotinib | Erlotinib + Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-in) | Sunitinib + Erlotinib | Erlotinib + Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/13 (38.5%) | 7/17 (41.2%) | 29/64 (45.3%) | 28/64 (43.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Thrombocytopenia | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Cardiac disorders | ||||||||
| Congestive cardiomyopathy | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Cardiopulmonary failure | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Tachycardia | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Abdominal pain | 0/13 (0%) | 1/17 (5.9%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Anal fistula | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Ascites | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Constipation | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Diarrhoea | 0/13 (0%) | 1/17 (5.9%) | 5/64 (7.8%) | 1/64 (1.6%) | ||||
| Dysphagia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Femoral hernia, obstructive | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Gastrointestinal haemorrhage | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Ileus | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Intestinal obstruction | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Nausea | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Oesophagitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pancreatitis acute | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Vomiting | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 4/64 (6.3%) | ||||
| Oesophageal stenosis | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Disease progression | 1/13 (7.7%) | 2/17 (11.8%) | 8/64 (12.5%) | 8/64 (12.5%) | ||||
| Fatigue | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Mucosal inflammation | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Non-cardiac chest pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pyrexia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Thrombosis in device | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Ulcer haemorrhage | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholecystitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Jaundice | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Bronchitis bacterial | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Bronchopneumonia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Gastroenteritis | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Infection | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pneumonia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pneumonia fungal | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Pneumonia staphylococcal | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Sepsis | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Urinary tract infection | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Ankle fracture | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Dehydration | 0/13 (0%) | 1/17 (5.9%) | 1/64 (1.6%) | 3/64 (4.7%) | ||||
| Failure to thrive | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Hypercalcaemia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Hyponatraemia | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Back pain | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Bone pain | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Musculoskeletal pain | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Nervous system disorders | ||||||||
| Depressed level of consciousness | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Diabetic hyperosmolar coma | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Haemorrhage intracranial | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Hypoglycaemic coma | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Nervous system disorder | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Psychiatric disorders | ||||||||
| Completed suicide | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Mental status changes | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Renal failure | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disease | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Dyspnoea | 2/13 (15.4%) | 0/17 (0%) | 2/64 (3.1%) | 1/64 (1.6%) | ||||
| Epistaxis | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Haemoptysis | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Pleural effusion | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pulmonary embolism | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Pulmonary oedema | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Respiratory failure | 1/13 (7.7%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Pleurisy | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Vascular disorders | ||||||||
| Ischaemia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Thrombophlebitis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Sunitinib + Erlotinib (Original Lead-In) | Sunitinib + Erlotinib (Amended Lead-in) | Sunitinib + Erlotinib | Erlotinib + Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/13 (100%) | 15/17 (88.2%) | 60/64 (93.8%) | 61/64 (95.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 3/13 (23.1%) | 1/17 (5.9%) | 7/64 (10.9%) | 4/64 (6.3%) | ||||
| Leukopenia | 1/13 (7.7%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Neutropenia | 3/13 (23.1%) | 0/17 (0%) | 6/64 (9.4%) | 0/64 (0%) | ||||
| Thrombocytopenia | 1/13 (7.7%) | 0/17 (0%) | 8/64 (12.5%) | 0/64 (0%) | ||||
| Leukocytosis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Lymphopenia | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Cyanosis | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Sinus bradycardia | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Tachycardia | 0/13 (0%) | 1/17 (5.9%) | 1/64 (1.6%) | 3/64 (4.7%) | ||||
| Bundle branch block left | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Bundle branch block right | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Pericardial effusion | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Pericarditis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Sinus tachycardia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Dry eye | 0/13 (0%) | 0/17 (0%) | 4/64 (6.3%) | 3/64 (4.7%) | ||||
| Blepharitis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Conjunctivitis | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 3/64 (4.7%) | ||||
| Eye irritation | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Eye pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Eye pruritus | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Keratitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Lacrimation increased | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Periorbital oedema | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 2/13 (15.4%) | 1/17 (5.9%) | 7/64 (10.9%) | 4/64 (6.3%) | ||||
| Abdominal pain upper | 1/13 (7.7%) | 3/17 (17.6%) | 3/64 (4.7%) | 2/64 (3.1%) | ||||
| Constipation | 1/13 (7.7%) | 0/17 (0%) | 9/64 (14.1%) | 9/64 (14.1%) | ||||
| Diarrhoea | 10/13 (76.9%) | 9/17 (52.9%) | 37/64 (57.8%) | 22/64 (34.4%) | ||||
| Duodenogastric reflux | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Dyspepsia | 1/13 (7.7%) | 1/17 (5.9%) | 4/64 (6.3%) | 6/64 (9.4%) | ||||
| Flatulence | 1/13 (7.7%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Gastrooesophageal reflux disease | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Haemorrhoids | 2/13 (15.4%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Nausea | 5/13 (38.5%) | 1/17 (5.9%) | 22/64 (34.4%) | 15/64 (23.4%) | ||||
| Oral pain | 2/13 (15.4%) | 0/17 (0%) | 6/64 (9.4%) | 0/64 (0%) | ||||
| Stomatitis | 2/13 (15.4%) | 0/17 (0%) | 5/64 (7.8%) | 4/64 (6.3%) | ||||
| Vomiting | 3/13 (23.1%) | 2/17 (11.8%) | 13/64 (20.3%) | 14/64 (21.9%) | ||||
| Abdominal discomfort | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Abdominal distension | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Abnormal faeces | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Anal haemorrhage | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Anorectal discomfort | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Ascites | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Dry mouth | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Dysphagia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Gastritis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Gastrointestinal haemorrhage | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Gingival bleeding | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Gingival disorder | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Glossodynia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Haemorrhoidal haemorrhage | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Lip swelling | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Mouth cyst | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Oesophageal pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 3/13 (23.1%) | 0/17 (0%) | 2/64 (3.1%) | 3/64 (4.7%) | ||||
| Chest discomfort | 2/13 (15.4%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Chest pain | 1/13 (7.7%) | 0/17 (0%) | 2/64 (3.1%) | 7/64 (10.9%) | ||||
| Chills | 1/13 (7.7%) | 0/17 (0%) | 2/64 (3.1%) | 2/64 (3.1%) | ||||
| Fatigue | 8/13 (61.5%) | 2/17 (11.8%) | 29/64 (45.3%) | 33/64 (51.6%) | ||||
| Mucosal inflammation | 1/13 (7.7%) | 0/17 (0%) | 12/64 (18.8%) | 7/64 (10.9%) | ||||
| Oedema peripheral | 2/13 (15.4%) | 1/17 (5.9%) | 3/64 (4.7%) | 4/64 (6.3%) | ||||
| Pain | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Pyrexia | 4/13 (30.8%) | 1/17 (5.9%) | 3/64 (4.7%) | 6/64 (9.4%) | ||||
| Suprapubic pain | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Early satiety | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Facial pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| General physical health deterioration | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Influenza like illness | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Localised oedema | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Malaise | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Mucous membrane disorder | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Non-cardiac chest pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Oedema | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Thrombosis in device | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Hypertransaminasaemia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Infections and infestations | ||||||||
| Infection | 2/13 (15.4%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Nasopharyngitis | 0/13 (0%) | 1/17 (5.9%) | 1/64 (1.6%) | 4/64 (6.3%) | ||||
| Oral candidiasis | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Paronychia | 2/13 (15.4%) | 0/17 (0%) | 2/64 (3.1%) | 3/64 (4.7%) | ||||
| Pneumonia | 1/13 (7.7%) | 0/17 (0%) | 3/64 (4.7%) | 3/64 (4.7%) | ||||
| Respiratory tract infection | 0/13 (0%) | 1/17 (5.9%) | 2/64 (3.1%) | 1/64 (1.6%) | ||||
| Sinusitis | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Urinary tract infection | 2/13 (15.4%) | 1/17 (5.9%) | 6/64 (9.4%) | 0/64 (0%) | ||||
| Abscess | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Candidiasis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Clostridium difficile colitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Conjunctivitis infective | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Cystitis | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 2/64 (3.1%) | ||||
| Fungal infection | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Gastroenteritis viral | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Herpes simplex | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Herpes zoster | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Influenza | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Lip infection | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Localised infection | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Nail infection | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Oral herpes | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Oral pustule | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Pneumonia primary atypical | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Pulmonary mycosis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Rash pustular | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Respiratory moniliasis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Superinfection | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Upper respiratory tract infection | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 1/64 (1.6%) | ||||
| Bronchitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arthropod bite | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Contusion | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Eye injury | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Fall | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Heat stroke | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Rib fracture | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Aspartate aminotransferase increased | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Blood alkaline phosphatase increased | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Blood creatinine increased | 2/13 (15.4%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Haemoglobin decreased | 1/13 (7.7%) | 0/17 (0%) | 2/64 (3.1%) | 3/64 (4.7%) | ||||
| Platelet count decreased | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Vitamin B12 decreased | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Weight decreased | 1/13 (7.7%) | 0/17 (0%) | 10/64 (15.6%) | 6/64 (9.4%) | ||||
| White blood cell count decreased | 2/13 (15.4%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Blood bilirubin increased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Blood lactate dehydrogenase increased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Blood pressure increased | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Blood thyroid stimulating hormone decreased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Electrocardiogram QT prolonged | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Granulocyte count decreased | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| International normalised ratio increased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Lipase increased | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Liver function test abnormal | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Neutrophil count decreased | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Transaminases increased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Weight increased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| White blood cell count increased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 7/13 (53.8%) | 1/17 (5.9%) | 24/64 (37.5%) | 20/64 (31.3%) | ||||
| Dehydration | 5/13 (38.5%) | 2/17 (11.8%) | 4/64 (6.3%) | 0/64 (0%) | ||||
| Hyperglycaemia | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Hypoglycaemia | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Hypokalaemia | 2/13 (15.4%) | 1/17 (5.9%) | 6/64 (9.4%) | 4/64 (6.3%) | ||||
| Hypomagnesaemia | 3/13 (23.1%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Hypophosphataemia | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Hypercalcaemia | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 2/64 (3.1%) | ||||
| Hypercreatininaemia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Hypoalbuminaemia | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 1/64 (1.6%) | ||||
| Hypocalcaemia | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Hyponatraemia | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 3/64 (4.7%) | ||||
| Hypophagia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Vitamin B12 deficiency | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 3/13 (23.1%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Arthritis | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Back pain | 1/13 (7.7%) | 0/17 (0%) | 5/64 (7.8%) | 9/64 (14.1%) | ||||
| Bone pain | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Groin pain | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Muscle atrophy | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Musculoskeletal chest pain | 2/13 (15.4%) | 0/17 (0%) | 5/64 (7.8%) | 3/64 (4.7%) | ||||
| Myalgia | 1/13 (7.7%) | 0/17 (0%) | 2/64 (3.1%) | 1/64 (1.6%) | ||||
| Pain in extremity | 1/13 (7.7%) | 0/17 (0%) | 7/64 (10.9%) | 2/64 (3.1%) | ||||
| Arthropathy | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Bursitis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Fistula | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Flank pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Hypertrophic osteoarthropathy | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Mobility decreased | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Muscle spasms | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Muscular weakness | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Musculoskeletal pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 3/64 (4.7%) | ||||
| Neck pain | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 0/64 (0%) | ||||
| Trismus | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pain in jaw | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumour pain | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Nervous system disorders | ||||||||
| Ageusia | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Dizziness | 2/13 (15.4%) | 0/17 (0%) | 2/64 (3.1%) | 2/64 (3.1%) | ||||
| Dysgeusia | 4/13 (30.8%) | 1/17 (5.9%) | 12/64 (18.8%) | 6/64 (9.4%) | ||||
| Headache | 1/13 (7.7%) | 0/17 (0%) | 3/64 (4.7%) | 2/64 (3.1%) | ||||
| Paraesthesia | 1/13 (7.7%) | 0/17 (0%) | 3/64 (4.7%) | 4/64 (6.3%) | ||||
| Peripheral sensory neuropathy | 0/13 (0%) | 1/17 (5.9%) | 2/64 (3.1%) | 2/64 (3.1%) | ||||
| Somnolence | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Aphasia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Balance disorder | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Dysarthria | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Dyskinesia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Facial paresis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Hyperaesthesia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Hypoaesthesia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Lethargy | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Memory impairment | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Neuralgia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Neuropathy peripheral | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Peripheral motor neuropathy | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Spinal cord oedema | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Syncope | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Tremor | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 1/64 (1.6%) | ||||
| Vocal cord paralysis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 1/13 (7.7%) | 1/17 (5.9%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Depression | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Hallucination | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Insomnia | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 5/64 (7.8%) | ||||
| Agitation | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Confusional state | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Nervousness | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Restlessness | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Sleep disorder | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 2/64 (3.1%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 1/13 (7.7%) | 1/17 (5.9%) | 3/64 (4.7%) | 1/64 (1.6%) | ||||
| Haematuria | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Haemoglobinuria | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Micturition urgency | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Nephrolithiasis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Pollakiuria | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Proteinuria | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Renal failure | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Urinary hesitation | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Urinary retention | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Peyronie's disease | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Vulvovaginal dryness | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 6/13 (46.2%) | 2/17 (11.8%) | 13/64 (20.3%) | 9/64 (14.1%) | ||||
| Dysphonia | 1/13 (7.7%) | 0/17 (0%) | 3/64 (4.7%) | 1/64 (1.6%) | ||||
| Dyspnoea | 4/13 (30.8%) | 3/17 (17.6%) | 9/64 (14.1%) | 17/64 (26.6%) | ||||
| Dyspnoea exertional | 2/13 (15.4%) | 1/17 (5.9%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Epistaxis | 1/13 (7.7%) | 1/17 (5.9%) | 3/64 (4.7%) | 4/64 (6.3%) | ||||
| Haemoptysis | 0/13 (0%) | 2/17 (11.8%) | 4/64 (6.3%) | 3/64 (4.7%) | ||||
| Hypoxia | 0/13 (0%) | 1/17 (5.9%) | 0/64 (0%) | 0/64 (0%) | ||||
| Oropharyngeal pain | 2/13 (15.4%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Pleural effusion | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Productive cough | 1/13 (7.7%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Pulmonary haemorrhage | 0/13 (0%) | 1/17 (5.9%) | 5/64 (7.8%) | 4/64 (6.3%) | ||||
| Sinus disorder | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Alveolar proteinosis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Hiccups | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Increased upper airway secretion | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Lung infiltration | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Pleuritic pain | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 0/64 (0%) | ||||
| Pneumothorax | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Respiratory tract haemorrhage | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Sinus congestion | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 6/13 (46.2%) | 0/17 (0%) | 7/64 (10.9%) | 8/64 (12.5%) | ||||
| Alopecia | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 6/64 (9.4%) | ||||
| Dermatitis acneiform | 1/13 (7.7%) | 3/17 (17.6%) | 6/64 (9.4%) | 12/64 (18.8%) | ||||
| Dry skin | 1/13 (7.7%) | 1/17 (5.9%) | 20/64 (31.3%) | 17/64 (26.6%) | ||||
| Exfoliative rash | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 7/64 (10.9%) | ||||
| Palmar erythema | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/13 (0%) | 1/17 (5.9%) | 5/64 (7.8%) | 2/64 (3.1%) | ||||
| Plantar erythema | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Pruritus | 1/13 (7.7%) | 0/17 (0%) | 9/64 (14.1%) | 15/64 (23.4%) | ||||
| Rash | 6/13 (46.2%) | 7/17 (41.2%) | 27/64 (42.2%) | 19/64 (29.7%) | ||||
| Rash generalised | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Skin disorder | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 0/64 (0%) | ||||
| Skin exfoliation | 1/13 (7.7%) | 0/17 (0%) | 7/64 (10.9%) | 4/64 (6.3%) | ||||
| Skin toxicity | 0/13 (0%) | 3/17 (17.6%) | 0/64 (0%) | 0/64 (0%) | ||||
| Blister | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Decubitus ulcer | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Erythema | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Hyperhidrosis | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 2/64 (3.1%) | ||||
| Hypertrichosis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Nail disorder | 0/13 (0%) | 0/17 (0%) | 3/64 (4.7%) | 2/64 (3.1%) | ||||
| Night sweats | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Petechiae | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Rash erythematous | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Rash macular | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Rash maculo-papular | 0/13 (0%) | 0/17 (0%) | 2/64 (3.1%) | 0/64 (0%) | ||||
| Rash papular | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Rash pruritic | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Scab | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Skin fissures | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 1/64 (1.6%) | ||||
| Skin lesion | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Yellow skin | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 1/13 (7.7%) | 4/17 (23.5%) | 5/64 (7.8%) | 1/64 (1.6%) | ||||
| Hypotension | 1/13 (7.7%) | 0/17 (0%) | 3/64 (4.7%) | 1/64 (1.6%) | ||||
| Vena cava thrombosis | 1/13 (7.7%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Circulatory collapse | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
| Deep vein thrombosis | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 1/64 (1.6%) | ||||
| Haematoma | 0/13 (0%) | 0/17 (0%) | 0/64 (0%) | 2/64 (3.1%) | ||||
| Peripheral coldness | 0/13 (0%) | 0/17 (0%) | 1/64 (1.6%) | 0/64 (0%) | ||||
Limitations/Caveats
Due to rounding some percentages will not equal 100%
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer Clinical Trials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquires@Pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00265317
Other Study ID Numbers:
- A6181058
First Posted:
Dec 14, 2005
Last Update Posted:
Feb 6, 2013
Last Verified:
Jan 1, 2013