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Study Of SU011248 Plus Gefitinib (Iressa) In Patients With Advanced Renal Cell Carcinoma

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00113529
Collaborator
(none)
42
Enrollment
3
Locations
1
Arm
48
Duration (Months)
14
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the maximum tolerated dose and overall safety and tolerability of sunitinib [SU011248] administered in combination with gefitinib (Iressa) for the treatment of patients with metastatic renal cell carcinoma (Phase 1). To assess antitumor activity of the combination of gefitinib and sunitinib (Phase 2).

Condition or Disease Intervention/Treatment Phase
  • Drug: Gefitinib + Sunitinib
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Safety And Pharmacokinetic Study Of SU011248 In Combination With Gefitinib (Iressa) In Patients With Metastatic Renal Cell Carcinoma
Study Start Date :
Oct 1, 2004
Actual Primary Completion Date :
Sep 1, 2007
Actual Study Completion Date :
Oct 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sunitinib + Gefitinib

Phase 1 - 37.5 mg Sunitinib 4/2 Schedule + 250 mg Gefitinib; 50 mg Sunitinib + 250 mg Gefitinib Phase 2 - 37.5 mg Sunitinib 4/2 Schedule + 250 mg Gefitinib

Drug: Gefitinib + Sunitinib
Until disease progression or unacceptable toxicity.
Other Names:
  • Iressa, SU011248, SUTENT

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) [From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter]

      Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

    Secondary Outcome Measures

    1. Time to Tumor Response (TTR) [From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter]

      TTR was defined as the time from date of the first dose of study medication to first documentation of objective tumor response (CR or PR). For subjects proceeding from PR to CR, the onset of PR was taken as the onset of response. If lesion assessment data included more than 1 date, the first date was used. TTR was calculated as (first event date minus first dose date +1)/7. TTR was calculated based on the subgroup of subjects with a baseline disease assessment, who had the correct histological cancer type, and had a confirmed objective tumor response. Kaplan-Meier method was used.

    2. Duration of Response (DR) [From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death due to cancer]

      DR was defined as the time from start of the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as (the end date for DR minus first CR or PR that was subsequently confirmed +1)/7. DR was calculated for the subgroup of subjects with an objective tumor response (CR or PR).

    3. Time to Tumor Progression (TTP) [From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter]

      TTP was defined as the time from the date of first dose of study medication to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.

    4. Overall Survival (OS) [From start of study treatment until death]

      OS was defined as the time from date of the first dose of study medication to date of death due to any cause. OS (in weeks) is calculated as (date of death minus first dose date +1)/7. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose had their survival times censored at 1 day. Kaplan-Meier method was used.

    5. Progression-Free Survival (PFS) [From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death]

      PFS was defined as the time from the date of first dose of study medication to the date of first documentation of tumor progression or death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.

    6. Probability of Survival at One Year [From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year]

      Survival rate was defined as the percentage of subjects alive at 1 year after the date of first administration of study medication. Survival rate was estimated using the Kaplan-Meier method.

    7. VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline [Baseline (Cycle 1, Day 1)]

      Concentration of VEGF at baseline.

    8. VEGF Ratio to Baseline at Each Time Point [Baseline to Cycle 3, Day 28 inclusive]

      VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).

    9. VEGF-C Concentration at Baseline [Baseline (Cycle 1, Day 1)]

      Concentration of VEGF-C at baseline.

    10. VEGF-C Ratio to Baseline at Each Time Point [Baseline to Cycle 3, Day 28 inclusive]

      VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline).

    11. Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline [Baseline (Cycle 1, Day 1)]

      Concentration of sVEGFR2 at baseline.

    12. sVEGFR2 Ratio to Baseline at Each Time Point [Baseline to Cycle 3, Day 28 inclusive]

      sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).

    13. Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline [Baseline (Cycle 1, Day 1)]

      Concentration of sVEGFR3 at baseline.

    14. sVEGFR3 Ratio to Baseline at Each Time Point [Baseline to Cycle 3, Day 28 inclusive]

      sVEGFR3 concentration at each time point divided by sVEGFR3 concentration at baseline (ratio to baseline).

    15. Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGF level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    16. Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFC level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    17. Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFR2 level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    18. Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFR3 level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    19. Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGF level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    20. Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFC level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    21. Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFR2 level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    22. Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFR3 level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    23. Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGF level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    24. Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFC level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    25. Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFR2 level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    26. Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median [Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive]

      Change = median VEGFR3 level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).

    27. Trough Plasma Concentrations (Ctrough) of Sunitinib [prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)]

    28. Ctrough of SU-012662 (Sunitinib's Metabolite) [prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)]

    29. Ctrough of Gefitinib [prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically confirmed renal cell carcinoma with metastases

    • Evidence of unidimensionally measurable disease

    • Failure of 1 prior immunotherapy or no prior systemic therapy for metastatic RCC

    Exclusion Criteria:

    • RCC without any clear (conventional) cell component

    • History of or known brain metastases

    • Uncontrolled hypertension or other significant cardiac events within the 12 months prior to study entry

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Ann Arbor Michigan United States 48109
    2 Pfizer Investigational Site New York New York United States 10021
    3 Pfizer Investigational Site Philadelphia Pennsylvania United States 19111-2497

    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:
    NCT00113529
    Other Study ID Numbers:
    • A6181038
    First Posted:
    Jun 9, 2005
    Last Update Posted:
    Aug 29, 2011
    Last Verified:
    Aug 1, 2011
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Renal Cell
    Sunitinib
    Gefitinib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail There were 11 subjects enrolled in Phase 1. Phase 2 included 4 subjects from Phase 1 (37.5 mg sunitinib Cohort) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib Cohort), for a total of 35 subjects.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 milligrams (mg) or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Period Title: Overall Study
    STARTED 35
    COMPLETED 1
    NOT COMPLETED 34

    Baseline Characteristics

    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Overall Participants 35
    Age, Customized (participants) [Number]
    < 65 years
    19
    54.3%
    > = 65 years
    16
    45.7%
    Sex: Female, Male (Count of Participants)
    Female
    9
    25.7%
    Male
    26
    74.3%

    Outcome Measures

    1. Primary Outcome
    Title Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
    Description Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
    Time Frame From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) = all subjects enrolled in the study that received at least 1 dose of study medication (sunitinib or gefitinib).
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 35
    Number [participants]
    13
    37.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Objective Response Rate (ORR) (percent)
    Estimated Value 37.1
    Confidence Interval () 95%
    21.5 to 55.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments ORR=proportion of subjects with confirmed CR or PR, relative to total subjects who received at least 1 dose of study medication, had a baseline disease assessment, and had the correct histological cancer type.
    2. Secondary Outcome
    Title Time to Tumor Response (TTR)
    Description TTR was defined as the time from date of the first dose of study medication to first documentation of objective tumor response (CR or PR). For subjects proceeding from PR to CR, the onset of PR was taken as the onset of response. If lesion assessment data included more than 1 date, the first date was used. TTR was calculated as (first event date minus first dose date +1)/7. TTR was calculated based on the subgroup of subjects with a baseline disease assessment, who had the correct histological cancer type, and had a confirmed objective tumor response. Kaplan-Meier method was used.
    Time Frame From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = those who had a confirmed response on study.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 13
    Median (95% Confidence Interval) [weeks]
    16.0
    3. Secondary Outcome
    Title Duration of Response (DR)
    Description DR was defined as the time from start of the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as (the end date for DR minus first CR or PR that was subsequently confirmed +1)/7. DR was calculated for the subgroup of subjects with an objective tumor response (CR or PR).
    Time Frame From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death due to cancer

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = those who had a response and subsequent progression or death due to any cause while on study.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 4
    Median (Full Range) [weeks]
    52.2
    4. Secondary Outcome
    Title Time to Tumor Progression (TTP)
    Description TTP was defined as the time from the date of first dose of study medication to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.
    Time Frame From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = those who progressed on study.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 19
    Median (95% Confidence Interval) [weeks]
    48.4
    5. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from date of the first dose of study medication to date of death due to any cause. OS (in weeks) is calculated as (date of death minus first dose date +1)/7. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose had their survival times censored at 1 day. Kaplan-Meier method was used.
    Time Frame From start of study treatment until death

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = subjects who died.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 12
    Median (Full Range) [weeks]
    49.5
    6. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description PFS was defined as the time from the date of first dose of study medication to the date of first documentation of tumor progression or death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.
    Time Frame From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = those who progressed or died due to any cause while on study.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 19
    Median (95% Confidence Interval) [weeks]
    48.4
    7. Secondary Outcome
    Title Probability of Survival at One Year
    Description Survival rate was defined as the percentage of subjects alive at 1 year after the date of first administration of study medication. Survival rate was estimated using the Kaplan-Meier method.
    Time Frame From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 35
    Number [probability]
    82.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter probability
    Estimated Value 82.4
    Confidence Interval () 95%
    64.9 to 91.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline
    Description Concentration of VEGF at baseline.
    Time Frame Baseline (Cycle 1, Day 1)

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Mean (Standard Deviation) [pg/mL]
    63.79
    (43.437)
    9. Secondary Outcome
    Title VEGF Ratio to Baseline at Each Time Point
    Description VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).
    Time Frame Baseline to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 28 (n=29)
    2.29
    (1.269)
    Cycle 2, Day 1 (n=26)
    1.65
    (1.951)
    Cycle 2, Day 28 (n=23)
    2.65
    (1.956)
    Cycle 3, Day 1 (n=22)
    1.93
    (1.872)
    Cycle 3, Day 28 (n=20)
    2.26
    (1.195)
    10. Secondary Outcome
    Title VEGF-C Concentration at Baseline
    Description Concentration of VEGF-C at baseline.
    Time Frame Baseline (Cycle 1, Day 1)

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Mean (Standard Deviation) [pg/mL]
    725.82
    (533.798)
    11. Secondary Outcome
    Title VEGF-C Ratio to Baseline at Each Time Point
    Description VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline).
    Time Frame Baseline to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 28 (n=29)
    0.93
    (0.433)
    Cycle 2, Day 1 (n=26)
    0.86
    (0.315)
    Cycle 2, Day 28 (n=23)
    1.01
    (0.585)
    Cycle 3, Day 1 (n=22)
    1.09
    (0.573)
    Cycle 3, Day 28 (n=20)
    0.93
    (0.452)
    12. Secondary Outcome
    Title Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline
    Description Concentration of sVEGFR2 at baseline.
    Time Frame Baseline (Cycle 1, Day 1)

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Mean (Standard Deviation) [pg/mL]
    10525.0
    (2198.017)
    13. Secondary Outcome
    Title sVEGFR2 Ratio to Baseline at Each Time Point
    Description sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).
    Time Frame Baseline to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 28 (n=29)
    0.64
    (0.130)
    Cycle 2, Day 1 (n=26)
    0.82
    (0.181)
    Cycle 2, Day 28 (n=23)
    0.63
    (0.151)
    Cycle 3, Day 1 (n=22)
    0.75
    (0.154)
    Cycle 3, Day 28 (n=20)
    0.64
    (0.217)
    14. Secondary Outcome
    Title Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline
    Description Concentration of sVEGFR3 at baseline.
    Time Frame Baseline (Cycle 1, Day 1)

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Mean (Standard Deviation) [pg/mL]
    48355.48
    (19623.342)
    15. Secondary Outcome
    Title sVEGFR3 Ratio to Baseline at Each Time Point
    Description sVEGFR3 concentration at each time point divided by sVEGFR3 concentration at baseline (ratio to baseline).
    Time Frame Baseline to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with levels of soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 28 (n=29)
    0.41
    (0.185)
    Cycle 2, Day 1 (n=26)
    0.96
    (0.506)
    Cycle 2, Day 28 (n=23)
    0.52
    (0.413)
    Cycle 3, Day 1 (n=22)
    0.89
    (0.453)
    Cycle 3, Day 28 (n=20)
    0.38
    (0.211)
    16. Secondary Outcome
    Title Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
    Description Change = median VEGF level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 1 (CR or PR or SD, n=22)
    40.70
    Cycle 1, Day 1 (PD, n=5)
    94.50
    Cycle 1, Day 28 (CR or PR or SD, n=22)
    2.31
    Cycle 1, Day 28 (PD, n=4)
    1.94
    Cycle 2, Day 1 (CR or PR or SD, n=22)
    1.05
    Cycle 2, Day 1 (PD, n=3)
    1.01
    Cycle 2, Day 28 (CR or PR or SD, n=21)
    2.26
    Cycle 2, Day 28 (PD, n=2)
    2.30
    Cycle 3, Day 1 (CR or PR or SD, n=20)
    1.33
    Cycle 3, Day 1(PD, n=2)
    0.91
    Cycle 3, Day 28 (CR or PR or SD, n=20)
    1.87
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.075
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.749
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.834
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.332
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    17. Secondary Outcome
    Title Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
    Description Change = median VEGFC level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 1 (CR or PR or SD, n=22)
    561.20
    Cycle 1, Day 1 (PD, n=5)
    751.30
    Cycle 1, Day 28 (CR or PR or SD, n=22)
    0.95
    Cycle 1, Day 28 (PD, n=4)
    0.71
    Cycle 2, Day 1 (CR or PR or SD, n=22)
    0.90
    Cycle 2, Day 1 (PD, n=3)
    0.80
    Cycle 2, Day 28 (CR or PR or SD, n=21)
    0.84
    Cycle 2, Day 28 (PD, n=2)
    1.19
    Cycle 3, Day 1 (CR or PR or SD, n=20)
    1.04
    Cycle 3, Day 1(PD, n=2)
    0.69
    Cycle 3, Day 28 (CR or PR or SD, n=20)
    0.93
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.473
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.286
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.277
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.956
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.278
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    18. Secondary Outcome
    Title Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
    Description Change = median VEGFR2 level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 1 (CR or PR or SD, n=22)
    10041.50
    Cycle 1, Day 1 (PD, n=5)
    9760.00
    Cycle 1, Day 28 (CR or PR or SD, n=22)
    0.59
    Cycle 1, Day 28 (PD, n=4)
    0.68
    Cycle 2, Day 1 (CR or PR or SD, n=22)
    0.79
    Cycle 2, Day 1 (PD, n=3)
    0.69
    Cycle 2, Day 28 (CR or PR or SD, n=21)
    0.62
    Cycle 2, Day 28 (PD, n=2)
    0.62
    Cycle 3, Day 1 (CR or PR or SD, n=20)
    0.74
    Cycle 3, Day 1(PD, n=2)
    0.73
    Cycle 3, Day 28 (CR or PR or SD, n=20)
    0.59
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.275
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.227
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    19. Secondary Outcome
    Title Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
    Description Change = median VEGFR3 level at each specified time point for subjects with tumor response (CR or PR or [SD > = 6 weeks] versus PD) minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 31
    Cycle 1, Day 1 (CR or PR or SD, n=22)
    43325.00
    Cycle 1, Day 1 (PD, n=5)
    57300.00
    Cycle 1, Day 28 (CR or PR or SD, n=22)
    0.41
    Cycle 1, Day 28 (PD, n=4)
    0.34
    Cycle 2, Day 1 (CR or PR or SD, n=22)
    0.87
    Cycle 2, Day 1 (PD, n=3)
    0.71
    Cycle 2, Day 28 (CR or PR or SD, n=21)
    0.41
    Cycle 2, Day 28 (PD, n=2)
    1.32
    Cycle 3, Day 1 (CR or PR or SD, n=20)
    0.85
    Cycle 3, Day 1(PD, n=2)
    1.84
    Cycle 3, Day 28 (CR or PR or SD, n=20)
    0.37
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.435
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.722
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.645
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.140
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.046
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    20. Secondary Outcome
    Title Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
    Description Change = median VEGF level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for PFS (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (PFS >= Median, n=5)
    59.30
    Cycle 1, Day 1 (PFS < Median, n=11)
    44.70
    Cycle 1, Day 28 (PFS >= Median, n=5)
    2.32
    Cycle 1, Day 28 (PFS < Median, n=10)
    2.28
    Cycle 2, Day 1 (PFS >= Median, n=5)
    0.75
    Cycle 2, Day 1 (PFS < Median, n=9)
    1.06
    Cycle 2, Day 28 (PFS >= Median, n=5)
    1.91
    Cycle 2, Day 28 (PFS < Median, n=8)
    2.66
    Cycle 3, Day 1 (PFS >= Median, n=5)
    1.04
    Cycle 3, Day 1 (PFS < Median, n=8)
    1.60
    Cycle 3, Day 28 (PFS >= Median, n=5)
    1.79
    Cycle 3, Day 28 (PFS < Median, n=6)
    2.31
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.734
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.854
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.230
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.067
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.164
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.121
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    21. Secondary Outcome
    Title Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
    Description Change = median VEGFC level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for PFS (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (PFS >= Median, n=5)
    650.80
    Cycle 1, Day 1 (PFS < Median, n=11)
    532.70
    Cycle 1, Day 28 (PFS >= Median, n=5)
    0.76
    Cycle 1, Day 28 (PFS < Median, n=10)
    0.99
    Cycle 2, Day 1 (PFS >= Median, n=5)
    0.80
    Cycle 2, Day 1 (PFS < Median, n=9)
    1.00
    Cycle 2, Day 28 (PFS >= Median, n=5)
    0.84
    Cycle 2, Day 28 (PFS < Median, n=8)
    1.17
    Cycle 3, Day 1 (PFS >= Median, n=5)
    0.70
    Cycle 3, Day 1 (PFS < Median, n=8)
    1.05
    Cycle 3, Day 28 (PFS >= Median, n=5)
    0.90
    Cycle 3, Day 28 (PFS < Median, n=6)
    1.22
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.734
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.462
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.423
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.510
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.608
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.121
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    22. Secondary Outcome
    Title Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
    Description Change = median VEGFR2 level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for PFS (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (PFS >= Median, n=5)
    9100.00
    Cycle 1, Day 1 (PFS < Median, n=11)
    10145.00
    Cycle 1, Day 28 (PFS >= Median, n=5)
    0.56
    Cycle 1, Day 28 (PFS < Median, n=10)
    0.69
    Cycle 2, Day 1 (PFS >= Median, n=5)
    0.79
    Cycle 2, Day 1 (PFS < Median, n=9)
    0.78
    Cycle 2, Day 28 (PFS >= Median, n=5)
    0.56
    Cycle 2, Day 28 (PFS < Median, n=8)
    0.64
    Cycle 3, Day 1 (PFS >= Median, n=5)
    0.74
    Cycle 3, Day 1 (PFS < Median, n=8)
    0.75
    Cycle 3, Day 28 (PFS >= Median, n=5)
    0.52
    Cycle 3, Day 28 (PFS < Median, n=6)
    0.62
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.910
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.509
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.883
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.582
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    23. Secondary Outcome
    Title Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
    Description Change = median VEGFR3 level at each specified time point for subjects with tumor response PFS >= Median or PFS < Median minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for PFS (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (PFS >= Median, n=5)
    55100.00
    Cycle 1, Day 1 (PFS < Median, n=11)
    47500.00
    Cycle 1, Day 28 (PFS >= Median, n=5)
    0.29
    Cycle 1, Day 28 (PFS < Median, n=10)
    0.44
    Cycle 2, Day 1 (PFS >= Median, n=5)
    0.86
    Cycle 2, Day 1 (PFS < Median, n=9)
    0.73
    Cycle 2, Day 28 (PFS >= Median, n=5)
    0.30
    Cycle 2, Day 28 (PFS < Median, n=8)
    0.47
    Cycle 3, Day 1 (PFS >= Median, n=5)
    0.65
    Cycle 3, Day 1 (PFS < Median, n=8)
    0.91
    Cycle 3, Day 28 (PFS >= Median, n=5)
    0.32
    Cycle 3, Day 28 (PFS < Median, n=6)
    0.49
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.428
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.075
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.019
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.124
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.055
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    24. Secondary Outcome
    Title Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
    Description Change = median VEGF level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for TTP (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (TTP >= Median, n=5)
    59.30
    Cycle 1, Day 1 (TTP < Median, n=11)
    44.70
    Cycle 1, Day 28 (TTP >= Median, n=5)
    2.32
    Cycle 1, Day 28 (TTP < Median, n=10)
    2.28
    Cycle 2, Day 1 (TTP >= Median, n=5)
    0.75
    Cycle 2, Day 1 (TTP < Median, n=9)
    1.06
    Cycle 2, Day 28 (TTP >= Median, n=5)
    1.91
    Cycle 2, Day 28 (TTP < Median, n=8)
    2.66
    Cycle 3, Day 1 (TTP >= Median, n=5)
    1.04
    Cycle 3, Day 1 (TTP < Median, n=8)
    1.60
    Cycle 3, Day 28 (TTP >= Median, n=5)
    1.79
    Cycle 3, Day 28 (TTP < Median, n=6)
    2.31
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.734
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.854
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.230
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.067
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.164
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.121
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    25. Secondary Outcome
    Title Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
    Description Change = median VEGFC level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for TTP (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (TTP >= Median, n=5)
    650.80
    Cycle 1, Day 1 (TTP < Median, n=11)
    532.70
    Cycle 1, Day 28 (TTP >= Median, n=5)
    0.76
    Cycle 1, Day 28 (TTP < Median, n=10)
    0.99
    Cycle 2, Day 1 (TTP >= Median, n=5)
    0.80
    Cycle 2, Day 1 (TTP < Median, n=9)
    1.00
    Cycle 2, Day 28 (TTP >= Median, n=5)
    0.84
    Cycle 2, Day 28 (TTP < Median, n=8)
    1.17
    Cycle 3, Day 1 (TTP >= Median, n=5)
    0.70
    Cycle 3, Day 1 (TTP < Median, n=8)
    1.05
    Cycle 3, Day 28 (TTP >= Median, n=5)
    0.90
    Cycle 3, Day 28 (TTP < Median, n=6)
    1.22
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.734
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.462
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.423
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.510
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.608
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.121
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    26. Secondary Outcome
    Title Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
    Description Change = median VEGFR2 level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for TTP (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (TTP >= Median, n=5)
    9100.00
    Cycle 1, Day 1 (TTP < Median, n=11)
    10145.00
    Cycle 1, Day 28 (TTP >= Median, n=5)
    0.56
    Cycle 1, Day 28 (TTP < Median, n=10)
    0.69
    Cycle 2, Day 1 (TTP >= Median, n=5)
    0.79
    Cycle 2, Day 1 (TTP < Median, n=9)
    0.78
    Cycle 2, Day 28 (TTP >= Median, n=5)
    0.56
    Cycle 2, Day 28 (TTP < Median, n=8)
    0.64
    Cycle 3, Day 1 (TTP >= Median, n=5)
    0.74
    Cycle 3, Day 1 (TTP < Median, n=8)
    0.75
    Cycle 3, Day 28 (TTP >= Median, n=5)
    0.52
    Cycle 3, Day 28 (TTP < Median, n=6)
    0.62
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.910
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.509
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.883
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.582
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    27. Secondary Outcome
    Title Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
    Description Change = median VEGFR3 level at each specified time point for subjects with tumor response TTP >= Median and TTP < Median minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality).
    Time Frame Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive

    Outcome Measure Data

    Analysis Population Description
    ITT. Number of participants analyzed = number of subjects evaluable for TTP (ie, those who died or had tumor progression) with baseline biomarker values. n=number of subjects with soluble protein biomarkers at baseline and at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 16
    Cycle 1, Day 1 (TTP >= Median, n=5)
    55100.00
    Cycle 1, Day 1 (TTP < Median, n=11)
    47500.00
    Cycle 1, Day 28 (TTP >= Median, n=5)
    0.29
    Cycle 1, Day 28 (TTP < Median, n=10)
    0.44
    Cycle 2, Day 1 (TTP >= Median, n=5)
    0.86
    Cycle 2, Day 1 (TTP < Median, n=9)
    0.73
    Cycle 2, Day 28 (TTP >= Median, n=5)
    0.30
    Cycle 2, Day 28 (TTP < Median, n=8)
    0.47
    Cycle 3, Day 1 (TTP >= Median, n=5)
    0.65
    Cycle 3, Day 1 (TTP < Median, n=8)
    0.91
    Cycle 3, Day 28 (TTP >= Median, n=5)
    0.32
    Cycle 3, Day 28 (TTP < Median, n=6)
    0.49
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.428
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 1, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.075
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 2, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.019
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.124
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
    Comments Cycle 3, Day 28
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.055
    Comments
    Method Wilcoxon Rank Sum Test
    Comments
    28. Secondary Outcome
    Title Trough Plasma Concentrations (Ctrough) of Sunitinib
    Description
    Time Frame prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) = the ITT population of subjects who had completed PK blood sampling for at least one day. n=number of subjects with trough plasma concentrations at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 35
    Cycle 1, Day 1 (n=35)
    1.57
    (9.263)
    Cycle 1, Day 28 (n=33)
    33.16
    (13.915)
    Cycle 2, Day 1 (n=28)
    3.25
    (3.209)
    Cycle 2, Day 28 (n=27)
    35.50
    (11.957)
    Cycle 3, Day 1 (n=25)
    3.71
    (3.335)
    Cycle 3, Day 28 (n=24)
    35.97
    (12.462)
    29. Secondary Outcome
    Title Ctrough of SU-012662 (Sunitinib's Metabolite)
    Description
    Time Frame prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)

    Outcome Measure Data

    Analysis Population Description
    PK = the ITT population of subjects who had completed PK blood sampling for at least one day. n=number of subjects with trough plasma concentrations at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 35
    Cycle 1, Day 1 (n=35)
    1.16
    (6.846)
    Cycle 1, Day 28 (n=33)
    16.21
    (9.381)
    Cycle 2, Day 1 (n=28)
    3.03
    (2.227)
    Cycle 2, Day 28 (n=27)
    15.25
    (6.310)
    Cycle 3, Day 1 (n=25)
    3.18
    (3.564)
    Cycle 3, Day 28 (n=24)
    14.56
    (8.019)
    30. Secondary Outcome
    Title Ctrough of Gefitinib
    Description
    Time Frame prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)

    Outcome Measure Data

    Analysis Population Description
    PK = the ITT population of subjects who had completed PK blood sampling for at least one day. n=number of subjects with trough plasma concentrations at the specified time point.
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    Measure Participants 35
    Cycle 1, Day 1 (n=35)
    0.00
    (0.000)
    Cycle 1, Day 28 (n=33)
    254.74
    (191.631)
    Cycle 2, Day 1 (n=24)
    328.91
    (280.286)
    Cycle 2, Day 28 (n=27)
    263.23
    (210.287)
    Cycle 3, Day 1 (n=26)
    293.14
    (277.288)
    Cycle 3, Day 28 (n=24)
    211.43
    (102.670)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Sunitinib + Gefitinib
    Arm/Group Description Phase 2 included 4 subjects from Phase 1 (37.5 mg or 50 mg sunitinib [administered on Cycle 1, Days 1, 9, 10, 20, 21, 28; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28] + 250 mg gefitinib [administered on Cycle 1, Days 10, 20, 21, 28, 42; Cycles 2 to 4, Days 1, 28; Cycles 5 plus, Days 1, 28]) and 31 from Phase 2 (37.5 mg sunitinib + 250 mg gefitinib [both administered on Cycle 1, Days 1, 14, 28; Cycles 2 to 4, Days 1, 28; Cycle 5 plus, Days 1, 28]), for a total of 35 subjects. A cycle = sunitinib given daily for 4 weeks followed by a 2-week off-treatment period.
    All Cause Mortality
    Sunitinib + Gefitinib
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Sunitinib + Gefitinib
    Affected / at Risk (%) # Events
    Total 11/35 (31.4%)
    Cardiac disorders
    Ventricular tachycardia 1/35 (2.9%)
    Myocardial ischaemia 1/35 (2.9%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 2/35 (5.7%)
    Rectal haemorrhage 1/35 (2.9%)
    Hepatobiliary disorders
    Cholecystitis 1/35 (2.9%)
    Investigations
    Blood magnesium decreased 1/35 (2.9%)
    Blood calcium increased 1/35 (2.9%)
    Nervous system disorders
    Syncope 1/35 (2.9%)
    Renal and urinary disorders
    Haematuria 1/35 (2.9%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/35 (2.9%)
    Epistaxis 1/35 (2.9%)
    Dyspnoea 1/35 (2.9%)
    Other (Not Including Serious) Adverse Events
    Sunitinib + Gefitinib
    Affected / at Risk (%) # Events
    Total 35/35 (100%)
    Blood and lymphatic system disorders
    Anaemia 3/35 (8.6%)
    Neutropenia 2/35 (5.7%)
    Thrombocytopenia 3/35 (8.6%)
    Gastrointestinal disorders
    Constipation 8/35 (22.9%)
    Diarrhoea 34/35 (97.1%)
    Dyspepsia 15/35 (42.9%)
    Flatulence 2/35 (5.7%)
    Gastrooesophageal reflux disease 3/35 (8.6%)
    Haemorrhoids 2/35 (5.7%)
    Nausea 16/35 (45.7%)
    Oral pain 2/35 (5.7%)
    Rectal haemorrhage 2/35 (5.7%)
    Stomatitis 15/35 (42.9%)
    Vomiting 10/35 (28.6%)
    General disorders
    Fatigue 30/35 (85.7%)
    Oedema peripheral 7/35 (20%)
    Pyrexia 4/35 (11.4%)
    Infections and infestations
    Sinusitis 2/35 (5.7%)
    Upper respiratory tract infection 3/35 (8.6%)
    Urinary tract infection 3/35 (8.6%)
    Investigations
    Alanine aminotransferase increased 3/35 (8.6%)
    Aspartate aminotransferase increased 2/35 (5.7%)
    Blood phosphorus decreased 2/35 (5.7%)
    Blood pressure increased 3/35 (8.6%)
    Ejection fraction decreased 2/35 (5.7%)
    Weight decreased 3/35 (8.6%)
    White blood cell count decreased 4/35 (11.4%)
    Metabolism and nutrition disorders
    Anorexia 8/35 (22.9%)
    Decreased appetite 5/35 (14.3%)
    Hyperglycaemia 2/35 (5.7%)
    Hypophosphataemia 2/35 (5.7%)
    Musculoskeletal and connective tissue disorders
    Back pain 2/35 (5.7%)
    Flank pain 3/35 (8.6%)
    Muscular weakness 2/35 (5.7%)
    Pain in extremity 5/35 (14.3%)
    Nervous system disorders
    Dizziness 2/35 (5.7%)
    Dysgeusia 12/35 (34.3%)
    Headache 4/35 (11.4%)
    Hypoaesthesia 3/35 (8.6%)
    Neuropathy 2/35 (5.7%)
    Paraesthesia 3/35 (8.6%)
    Peripheral sensory neuropathy 3/35 (8.6%)
    Syncope 2/35 (5.7%)
    Renal and urinary disorders
    Dysuria 2/35 (5.7%)
    Nocturia 2/35 (5.7%)
    Pollakiuria 3/35 (8.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 6/35 (17.1%)
    Dysphonia 2/35 (5.7%)
    Dyspnoea 2/35 (5.7%)
    Dyspnoea exertional 10/35 (28.6%)
    Epistaxis 8/35 (22.9%)
    Wheezing 2/35 (5.7%)
    Skin and subcutaneous tissue disorders
    Acne 4/35 (11.4%)
    Alopecia 4/35 (11.4%)
    Blister 3/35 (8.6%)
    Dermatitis acneiform 5/35 (14.3%)
    Dry skin 12/35 (34.3%)
    Erythema 4/35 (11.4%)
    Hyperkeratosis 2/35 (5.7%)
    Night sweats 2/35 (5.7%)
    Palmar-plantar erythrodysaesthesia syndrome 11/35 (31.4%)
    Rash 20/35 (57.1%)
    Skin exfoliation 3/35 (8.6%)
    Skin lesion 2/35 (5.7%)
    Vascular disorders
    Hypertension 5/35 (14.3%)

    Limitations/Caveats

    [Not Specified]

    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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 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 ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.govCallCenter@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00113529
    Other Study ID Numbers:
    • A6181038
    First Posted:
    Jun 9, 2005
    Last Update Posted:
    Aug 29, 2011
    Last Verified:
    Aug 1, 2011