Trial Of PF-00299804 In Patients With Advanced Refractory Lung Cancer
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00553254
Collaborator
(none)
55
3
1
77.3
18.3
0.2
Study Details
Study Description
Brief Summary
To assess the safety and efficacy of PF-00299804 in patients with advanced lung cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
55 participants
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1/2, OPEN-LABEL, SINGLE ARM TRIAL TO DETERMINE THE RECOMMENDED PHASE 2 DOSE AND EVALUATE THE EFFICACY OF PF-00299804 IN PATIENTS IN KOREA WITH KRAS WILD TYPE ADVANCED NSCLC, WHICH IS REFRACTORY TO CHEMOTHERAPY AND ERLOTINIB OR GEFITINIB
Actual Study Start Date
:
Feb 5, 2008
Actual Primary Completion Date
:
Aug 3, 2010
Actual Study Completion Date
:
Jul 17, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: PF-00299804
Single arm (no comparator) study, oral once daily dosing, dose escalation (it is a phase 1/2 study) until disease progression, unacceptable toxicity or withdrawal of consent
|
Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose (RP2D) - Phase 1 [Baseline up to Day 21]
The highest dose at which less than (<) 33 percent (%) of participants experienced dose-limiting toxicities (DLT) was to be designated as the maximum tolerated dose (MTD) as well as the RP2D. DLT was defined as any of the following events: Grade 3/4 (severe or life-threatening/ disabling adverse event [AE]) nausea, vomiting, or diarrhea (despite the use of adequate/maximal medical intervention and/or prophylaxis); Grade greater than or equal to (>=) 3 (severe or life-threatening/disabling AE or death related to AE) non-hematological toxicity; delayed (which delayed scheduled treatment for >14 days) recovery from toxicity related to treatment with PF-00299804; Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cells per cubic millimeter [cells/mm^3] for 5 or more consecutive days or febrile neutropenia [fever >=38.5 degrees Celsius with ANC <1000 cells/mm^3]); and Grade 4 thrombocytopenia (<25,000 cells/mm^3) or bleeding which required platelet transfusion.
- Progression-Free Survival (PFS) at Month 4 (PFS4m) - Phase 2 [Month 4]
PFS4m was defined as percent chance of being event free (event defined as progressive disease [PD] or death due to any cause, whichever occurred first) at 4 months. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Secondary Outcome Measures
- Progression-Free Survival (PFS) at Month 6 (PFS6m) - Phase 2 [Month 6]
PFS6m was defined as percent chance of being event free (event defined as PD or death due to any cause, whichever occurred first) at 6 months. Progression was defined using RECIST, as at least 20% increase in the sum of longest dimensions (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
- Overall Survival (OS) at Month 6 (OS6m) - Phase 2 [Month 6]
OS6m was defined as percent chance of being alive at Month 6.
- Percentage of Participants With Objective Response - Phase 1 [Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after end of treatment (EOT) (EOT: up to Day 506)]
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the longest dimensions (LDs) of target lesion, taking as reference the baseline sum LD, associated to non-progressive disease response for non-target lesions. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
- Soluble Protein Biomarkers Level [Cycle 1 Day 1 (C1D1, Baseline), Day 1 of each odd-numbered cycle up to Cycle 17 for both Phase 1 and Phase 2]
Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (epidermal growth factor receptor [EGFR], HER2). These measurements were determined by enzyme-linked immunosorbent assay (ELISA). The data for all Phase 1 participants was combined for this outcome.
- Number of Participants With Epidermal Growth Factor Receptor (EGFR), Kirsten Rat Sarcoma (KRAS), and Human Epidermal Growth Factor Receptor-2 (HER2) Mutation Status [Screening]
Tumor tissue was analyzed at a sponsor-designated laboratory to investigate EGFR, KRAS and HER2 status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". The data for all Phase 1 participants was combined for this outcome.
- Maximum Observed Plasma Concentration (Cmax) of PF-00299804 30 mg and PF-00299804 45 mg [0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9 for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2]
Data in "PF-00299804 45 mg" treatment arm at Cycle 0 Day -9 (C0D-9) represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00299804 30 mg and PF-00299804 45 mg [0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2]
Data in "PF-00299804 45 mg" treatment arm at C0D-9 represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2.
- Plasma Decay Half-Life (t1/2) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 [0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9)]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Area Under the Curve From Time Zero to 24 Hour Post-Dose (AUC0-24) of PF-00299804 30 mg and PF-00299804 45 mg [0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2]
AUC0-24: Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post dose. Data in "PF- 00299804 45 mg" treatment arm at C0D-9 represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2.
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00299804 30 mg and PF-00299804 45 mg- Phase 1 [0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9]
AUClast: Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration.
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 [0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9]
AUCinf: Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
- Accumulation Ratio (Rac) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 [0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C0D-9, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14]
Rac was calculated by dividing AUC0-24 (C1D14) by AUC0-24 (C0D-9).
- Average Plasma Concentration (Cavg) of PF-00299804 30 mg and PF-00299804 45 mg [0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2]
Data in "PF-00299804 45 mg" treatment arm represents participants from both Phase 1 and Phase 2.
- Linearity Ratio (Rss) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 [0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14]
Rss was calculated by dividing AUC0-24 (C1D14) by AUCinf (C0D-9).
- Minimum Observed Plasma Trough Concentration (Ctrough) of PF-00299804 30 mg and PF-00299804 45 mg [0 hours (pre-dose) on C2D1, C3D1, C4D1]
Data in "PF-00299804 45 mg" treatment arm represents participants from both Phase 1 and Phase 2.
- Number of Participants With Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Phase 2 [Baseline up to end of treatment (up to Day 889)]
EORTC QLQ-C30: included global health status/quality of life (QoL), functional (Fn) scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Scores were averaged, transformed to 0-100 scale; higher score for Global Qol/Fn scales=better level of QoL/functioning or higher score for symptom scales/items=greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline: for Global QoL/Fn scales >=10; for symptom scale/item <=-10), Worsened (if average scales change from baseline: for Global QoL/Fn scales <=-10; for symptom scale/item >=10), and Stable (if average scales change from baseline >-10 but <10 for Global QoL/Fn scales and symptom scale/item) and participants in each category are reported.
- Number of Participants With Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Phase 2 [Baseline up to end of treatment (up to Day 889)]
EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline <=-10), Worsened (if average scales change from baseline >=10), and Stable (if average scales change from baseline >-10 but <10) and participants in each category are reported.
- Dermatology Life Quality Index (DLQI) Total Score - Phase 2 [C1D1 (baseline), D1 of each subsequent cycle up to C44]
DLQI: 10-item questionnaire to measure how much the participant's skin problem has impacted their life over the previous week. All questions were answered on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much/prevented work or studying). The DLQI was calculated by summing the score of each question and ranged from 0 to 30, where higher scores indicate more quality of life impairment.
- Best Overall Response (BOR) - Phase 2 [Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after EOT (EOT: up to Day 1723)]
Number of participants with BOR according to RECIST: CR= disappearance of all target and non-target lesions. PR= at least 30% decrease in sum of LDs of target lesion, taking as reference baseline sum LD, associated to non-progressive disease response for non-target lesions. Stable/no response= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Objective progression= at least a 20% increase in sum of LDs of target lesions, taking as reference the smallest sum of LD recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
- Duration of Response (DR) [Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after EOT (EOT: up to Day 506 for Phase 1 and up to Day 1723 for Phase 2)]
Time in weeks from first documentation of objective tumor response to objective tumor progression or death due to any cause, whichever occurred first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Advanced NSCLC
-
Prior treatment with and failure of at least one regimen of chemotherapy and erlotinib or gefitinib
-
Prior treatment with no more than two chemotherapy regimens, including adjuvant treatment
-
Measurable disease
Exclusion Criteria:
-
Chemotherapy, radiotherapy, biological or investigational agents within 4 weeks of baseline disease assessment
-
Patients who lack of tolerance of erlotinib therapy
-
Patients with known brain Metastases
-
Patients with demonstrated history of or presence of interstitial lung disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Seoul National University Hospital, Department of Internal Medicine | Seoul | Korea, Republic of | 110-744 | |
| 2 | Severance Hospital, Yonsei University College of Medicine, Yonsei Cancer Center | Seoul | Korea, Republic of | 120-752 | |
| 3 | Samsung Medical Center, Department of Medicine | Seoul | Korea, Republic of | 135-710 |
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:
NCT00553254
Other Study ID Numbers:
- A7471003
First Posted:
Nov 4, 2007
Last Update Posted:
Oct 19, 2020
Last Verified:
Sep 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 | PF-00299804 45 mg - Phase 2 |
|---|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Period Title: Overall Study | |||
| STARTED | 6 | 6 | 43 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 6 | 43 |
Baseline Characteristics
| Arm/Group Title | PF-00299804 - Phase 1 All Participants | PF-00299804 45 mg - Phase 2 | Total |
|---|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 mg or 45 mg tablet orally on or before Day -9 followed by PF-00299804 30 mg or 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | Total of all reporting groups |
| Overall Participants | 12 | 43 | 55 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
52.6
(12.3)
|
57.0
(8.7)
|
56.0
(9.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
9
75%
|
23
53.5%
|
32
58.2%
|
| Male |
3
25%
|
20
46.5%
|
23
41.8%
|
Outcome Measures
| Title | Recommended Phase 2 Dose (RP2D) - Phase 1 |
|---|---|
| Description | The highest dose at which less than (<) 33 percent (%) of participants experienced dose-limiting toxicities (DLT) was to be designated as the maximum tolerated dose (MTD) as well as the RP2D. DLT was defined as any of the following events: Grade 3/4 (severe or life-threatening/ disabling adverse event [AE]) nausea, vomiting, or diarrhea (despite the use of adequate/maximal medical intervention and/or prophylaxis); Grade greater than or equal to (>=) 3 (severe or life-threatening/disabling AE or death related to AE) non-hematological toxicity; delayed (which delayed scheduled treatment for >14 days) recovery from toxicity related to treatment with PF-00299804; Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cells per cubic millimeter [cells/mm^3] for 5 or more consecutive days or febrile neutropenia [fever >=38.5 degrees Celsius with ANC <1000 cells/mm^3]); and Grade 4 thrombocytopenia (<25,000 cells/mm^3) or bleeding which required platelet transfusion. |
| Time Frame | Baseline up to Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all enrolled participants who received at least 1 dose of study medication. |
| Arm/Group Title | PF-00299804 - Phase 1 All Participants |
|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 mg or 45 mg tablet orally on or before Day -9 followed by PF-00299804 30 mg or 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 12 |
| Number [mg] |
45
|
| Title | Progression-Free Survival (PFS) at Month 4 (PFS4m) - Phase 2 |
|---|---|
| Description | PFS4m was defined as percent chance of being event free (event defined as progressive disease [PD] or death due to any cause, whichever occurred first) at 4 months. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time Frame | Month 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all enrolled participants. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 43 |
| Number (95% Confidence Interval) [percent chance of being event-free] |
47.2
|
| Title | Progression-Free Survival (PFS) at Month 6 (PFS6m) - Phase 2 |
|---|---|
| Description | PFS6m was defined as percent chance of being event free (event defined as PD or death due to any cause, whichever occurred first) at 6 months. Progression was defined using RECIST, as at least 20% increase in the sum of longest dimensions (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time Frame | Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all enrolled participants. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 43 |
| Number (95% Confidence Interval) [percent chance of being event-free] |
24.8
|
| Title | Overall Survival (OS) at Month 6 (OS6m) - Phase 2 |
|---|---|
| Description | OS6m was defined as percent chance of being alive at Month 6. |
| Time Frame | Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all enrolled participants. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 43 |
| Number (95% Confidence Interval) [percent chance of being alive] |
80.7
|
| Title | Percentage of Participants With Objective Response - Phase 1 |
|---|---|
| Description | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the longest dimensions (LDs) of target lesion, taking as reference the baseline sum LD, associated to non-progressive disease response for non-target lesions. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. |
| Time Frame | Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after end of treatment (EOT) (EOT: up to Day 506) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population included all enrolled participants who received at least 1 dose of study medication, had an adequate baseline tumor assessment, and had at least 1 on-study tumor assessment after first dosing. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 6 |
| Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
33.3
77.4%
|
| Title | Soluble Protein Biomarkers Level |
|---|---|
| Description | Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (epidermal growth factor receptor [EGFR], HER2). These measurements were determined by enzyme-linked immunosorbent assay (ELISA). The data for all Phase 1 participants was combined for this outcome. |
| Time Frame | Cycle 1 Day 1 (C1D1, Baseline), Day 1 of each odd-numbered cycle up to Cycle 17 for both Phase 1 and Phase 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Data was pre-specified in statistical analysis plan to be analyzed and summarized per phase. Number analyzed = participants evaluable at specified time-point. |
| Arm/Group Title | PF-00299804 - Phase 1 All Participants | PF-00299804 45 mg - Phase 2 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 mg or 45 mg tablet orally on or before Day -9 followed by PF-00299804 30 mg or 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 12 | 43 |
| EGFR: C1D1 |
58.57
(7.498)
|
57.41
(13.146)
|
| EGFR: C3D1 |
47.46
(7.845)
|
50.81
(11.465)
|
| EGFR: C5D1 |
46.76
(5.395)
|
58.87
(13.627)
|
| EGFR: C7D1 |
48.58
(NA)
|
55.83
(19.34)
|
| EGFR: C9D1 |
42.83
(NA)
|
50.32
(26.214)
|
| EGFR: C11D1 |
40.98
(NA)
|
63.69
(28.908)
|
| EGFR: C13D1 |
67.34
(NA)
|
73.26
(29.487)
|
| EGFR: C15D1 |
52
(NA)
|
49.45
(14.358)
|
| EGFR: C17D1 |
66.62
(NA)
|
57.95
(24.923)
|
| HER2: C1D1 |
9.51
(2.418)
|
9.54
(5.859)
|
| HER2: C3D1 |
8.85
(1.125)
|
8.36
(4.284)
|
| HER2: C5D1 |
9.63
(2.542)
|
9.29
(5.138)
|
| HER2: C7D1 |
6.7
(NA)
|
11.57
(5.342)
|
| HER2: C9D1 |
5.6
(NA)
|
8.49
(4.124)
|
| HER2: C11D1 |
6.3
(NA)
|
8.2
(4.122)
|
| HER2: C13D1 |
11.7
(NA)
|
9.51
(5.97)
|
| HER2: C15D1 |
7.4
(NA)
|
5.43
(1.99)
|
| HER2: C17D1 |
8.9
(NA)
|
6.27
(2.626)
|
| Title | Number of Participants With Epidermal Growth Factor Receptor (EGFR), Kirsten Rat Sarcoma (KRAS), and Human Epidermal Growth Factor Receptor-2 (HER2) Mutation Status |
|---|---|
| Description | Tumor tissue was analyzed at a sponsor-designated laboratory to investigate EGFR, KRAS and HER2 status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". The data for all Phase 1 participants was combined for this outcome. |
| Time Frame | Screening |
Outcome Measure Data
| Analysis Population Description |
|---|
| Biomarker analysis set: all enrolled participants who had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. Data was pre-specified in statistical analysis plan to be analyzed and summarized per phase. |
| Arm/Group Title | PF-00299804 - Phase 1 All Participants | PF-00299804 45 mg - Phase 2 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 mg or 45 mg tablet orally on or before Day -9 followed by PF-00299804 30 mg or 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 12 | 43 |
| EGFR Status: Wild Type |
3
25%
|
3
7%
|
| EGFR Status: Mutant |
2
16.7%
|
12
27.9%
|
| EGFR Status: Unknown |
7
58.3%
|
28
65.1%
|
| KRAS Status: Wild Type |
9
75%
|
29
67.4%
|
| KRAS Status: Mutant |
0
0%
|
0
0%
|
| KRAS Status: Unknown |
3
25%
|
14
32.6%
|
| HER2 Status: Wild Type |
0
0%
|
9
20.9%
|
| HER2 Status: Mutant |
0
0%
|
1
2.3%
|
| HER2 Status: Unknown |
12
100%
|
33
76.7%
|
| Title | Maximum Observed Plasma Concentration (Cmax) of PF-00299804 30 mg and PF-00299804 45 mg |
|---|---|
| Description | Data in "PF-00299804 45 mg" treatment arm at Cycle 0 Day -9 (C0D-9) represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2. |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9 for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK): all participants who received at least 1 dose of study drug and had at least 1 measured plasma concentration. "number analyzed"=participants evaluable for specified time-point. PK analysis was done by dose level instead of by phase. Participants started from the same dose level were combined together for PK analysis. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 during Phase 1 or PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles during Phase 2, until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 40 |
| C0D-9 |
13.34
(4.8205)
|
21.30
(12.356)
|
| C1D14 |
56.96
(20.572)
|
82.71
(38.788)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00299804 30 mg and PF-00299804 45 mg |
|---|---|
| Description | Data in "PF-00299804 45 mg" treatment arm at C0D-9 represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2. |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 measured plasma concentration. "number analyzed"=participants evaluable for specified time-point. PK analysis was done by dose level instead of by phase. Participants started from the same dose level were combined together for PK analysis. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 during Phase 1 or PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles during Phase 2, until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 40 |
| C0D-9 |
8.00
|
4.96
|
| C1D14 |
5.03
|
6.10
|
| Title | Plasma Decay Half-Life (t1/2) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on Cycle 0 Day -9 (C0D-9) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set for Phase 1 included all participants who received at least 1 dose of study medication and had at least 1 measured plasma concentration. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [hours] |
63.60
(30.271)
|
54.02
(13.461)
|
| Title | Area Under the Curve From Time Zero to 24 Hour Post-Dose (AUC0-24) of PF-00299804 30 mg and PF-00299804 45 mg |
|---|---|
| Description | AUC0-24: Area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post dose. Data in "PF- 00299804 45 mg" treatment arm at C0D-9 represents participants from Phase 1 only and at C1D14 represents participants from both Phase 1 and Phase 2. |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on Cycle 0 Day -9 (C0D-9) for Phase 1, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 measured plasma concentration. "number analyzed"=participants evaluable for specified time-point. PK analysis was done by dose level instead of by phase. Participants started from the same dose level were combined together for PK analysis. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 during Phase 1 or PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles during Phase 2, until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 40 |
| C0D-9 |
221.6
(87.063)
|
354.8
(153.31)
|
| C1D14 |
1075
(515.66)
|
1621
(664.87)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00299804 30 mg and PF-00299804 45 mg- Phase 1 |
|---|---|
| Description | AUClast: Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration. |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set for Phase 1 included all participants who received at least 1 dose of study medication and had at least 1 measured plasma concentration. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Standard Deviation) [ng*hr/mL] |
893.4
(516.50)
|
1248
(522.11)
|
| Title | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 |
|---|---|
| Description | AUCinf: Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set for Phase 1 included all participants who received at least 1 dose of study medication and had at least 1 measured plasma concentration. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 6 |
| Geometric Mean (Standard Deviation) [ng*hr/mL] |
1018
(593.51)
|
1348
(599.34)
|
| Title | Accumulation Ratio (Rac) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 |
|---|---|
| Description | Rac was calculated by dividing AUC0-24 (C1D14) by AUC0-24 (C0D-9). |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C0D-9, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set for Phase 1 included all participants who received at least 1 dose of study medication and had at least 1 measured plasma concentration. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [ratio] |
5.265
(2.2958)
|
5.682
(2.5752)
|
| Title | Average Plasma Concentration (Cavg) of PF-00299804 30 mg and PF-00299804 45 mg |
|---|---|
| Description | Data in "PF-00299804 45 mg" treatment arm represents participants from both Phase 1 and Phase 2. |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 for Phase 1 and 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 measured plasma concentration. PK analysis was done by dose level instead of by phase. Participants started from the same dose level were combined together for PK analysis. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 during Phase 1 or PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles during Phase 2, until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 40 |
| Geometric Mean (Standard Deviation) [ng/mL] |
44.78
(21.439)
|
67.52
(27.643)
|
| Title | Linearity Ratio (Rss) of PF-00299804 30 mg and PF-00299804 45 mg - Phase 1 |
|---|---|
| Description | Rss was calculated by dividing AUC0-24 (C1D14) by AUCinf (C0D-9). |
| Time Frame | 0 (pre-dose), 2, 4, 6, 8, 24, 72, 144, 216 hours post-dose on C0D-9, 0 (pre-dose), 2, 4, 6, 8, 24 hours post-dose on C1D14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set for Phase 1 included all participants who received at least 1 dose of study medication and had at least 1 measured plasma concentration. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [ratio] |
1.093
(0.3100)
|
1.442
(0.5661)
|
| Title | Minimum Observed Plasma Trough Concentration (Ctrough) of PF-00299804 30 mg and PF-00299804 45 mg |
|---|---|
| Description | Data in "PF-00299804 45 mg" treatment arm represents participants from both Phase 1 and Phase 2. |
| Time Frame | 0 hours (pre-dose) on C2D1, C3D1, C4D1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set included all participants who received at least 1 dose of study drug and had at least 1 measured plasma concentration. PK analysis was done by dose level instead of by phase. Participants started from the same dose level were combined together for PK analysis."number analyzed" = participants evaluable for specified time-point. |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg |
|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 during Phase 1 or PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles during Phase 2, until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 6 | 40 |
| C2D1 |
45.96
(31.061)
|
65.11
(33.673)
|
| C3D1 |
46.52
(23.329)
|
66.98
(32.354)
|
| C4D1 |
40.34
(24.527)
|
69.75
(37.584)
|
| Title | Number of Participants With Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Phase 2 |
|---|---|
| Description | EORTC QLQ-C30: included global health status/quality of life (QoL), functional (Fn) scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Scores were averaged, transformed to 0-100 scale; higher score for Global Qol/Fn scales=better level of QoL/functioning or higher score for symptom scales/items=greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline: for Global QoL/Fn scales >=10; for symptom scale/item <=-10), Worsened (if average scales change from baseline: for Global QoL/Fn scales <=-10; for symptom scale/item >=10), and Stable (if average scales change from baseline >-10 but <10 for Global QoL/Fn scales and symptom scale/item) and participants in each category are reported. |
| Time Frame | Baseline up to end of treatment (up to Day 889) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all enrolled participants. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 39 |
| Global QoL: Improved |
5
41.7%
|
| Global QoL: Worsened |
18
150%
|
| Global QoL: Stable |
16
133.3%
|
| Physical Functioning: Improved |
2
16.7%
|
| Physical Functioning: Worsened |
20
166.7%
|
| Physical Functioning: Stable |
17
141.7%
|
| Role Functioning: Improved |
2
16.7%
|
| Role Functioning: Worsened |
22
183.3%
|
| Role Functioning: Stable |
15
125%
|
| Cognitive Functioning: Improved |
4
33.3%
|
| Cognitive Functioning: Worsened |
17
141.7%
|
| Cognitive Functioning: Stable |
18
150%
|
| Emotional Functioning: Improved |
2
16.7%
|
| Emotional Functioning: Worsened |
16
133.3%
|
| Emotional Functioning: Stable |
21
175%
|
| Social Functioning: Improved |
6
50%
|
| Social Functioning: Worsened |
15
125%
|
| Social Functioning: Stable |
18
150%
|
| Fatigue: Improved |
3
25%
|
| Fatigue: Worsened |
20
166.7%
|
| Fatigue: Stable |
16
133.3%
|
| Pain: Improved |
8
66.7%
|
| Pain: Worsened |
15
125%
|
| Pain: Stable |
16
133.3%
|
| Nausea and Vomiting: Improved |
4
33.3%
|
| Nausea and Vomiting: Worsened |
10
83.3%
|
| Nausea and Vomiting: Stable |
25
208.3%
|
| Dyspnea: Improved |
7
58.3%
|
| Dyspnea: Worsened |
16
133.3%
|
| Dyspnea: Stable |
16
133.3%
|
| Loss of Appetite: Improved |
6
50%
|
| Loss of Appetite: Worsened |
24
200%
|
| Loss of Appetite: Stable |
9
75%
|
| Insomnia: Improved |
9
75%
|
| Insomnia: Worsened |
12
100%
|
| Insomnia: Stable |
18
150%
|
| Constipation: Improved |
9
75%
|
| Constipation: Worsened |
8
66.7%
|
| Constipation: Stable |
22
183.3%
|
| Diarrhea: Improved |
0
0%
|
| Diarrhea: Worsened |
36
300%
|
| Diarrhea: Stable |
3
25%
|
| Financial Difficulties: Improved |
10
83.3%
|
| Financial Difficulties: Worsened |
9
75%
|
| Financial Difficulties: Stable |
20
166.7%
|
| Title | Number of Participants With Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Phase 2 |
|---|---|
| Description | EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline <=-10), Worsened (if average scales change from baseline >=10), and Stable (if average scales change from baseline >-10 but <10) and participants in each category are reported. |
| Time Frame | Baseline up to end of treatment (up to Day 889) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all enrolled participants. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure. Medicine for pain was not summarized because a more comprehensive and reliable summary of concomitant medications was reported separately. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 39 |
| Dyspnoea: Improved |
10
83.3%
|
| Dyspnoea: Worsened |
16
133.3%
|
| Dyspnoea: Stable |
13
108.3%
|
| Coughing: Improved |
9
75%
|
| Coughing: Worsened |
11
91.7%
|
| Coughing: Stable |
19
158.3%
|
| Haemoptysis: Improved |
0
0%
|
| Haemoptysis: Worsened |
5
41.7%
|
| Haemoptysis: Stable |
34
283.3%
|
| Sore mouth: Improved |
1
8.3%
|
| Sore mouth: Worsened |
33
275%
|
| Sore mouth: Stable |
5
41.7%
|
| Dysphagia: Improved |
4
33.3%
|
| Dysphagia: Worsened |
19
158.3%
|
| Dysphagia: Stable |
16
133.3%
|
| Peripheral: Improved |
9
75%
|
| Peripheral: Worsened |
10
83.3%
|
| Peripheral: Stable |
20
166.7%
|
| Alopecia: Improved |
7
58.3%
|
| Alopecia: Worsened |
11
91.7%
|
| Alopecia: Stable |
21
175%
|
| Pain in chest: Improved |
10
83.3%
|
| Pain in chest: Worsened |
10
83.3%
|
| Pain in chest: Stable |
19
158.3%
|
| Pain in arm or Shoulder: Improved |
16
133.3%
|
| Pain in arm or Shoulder: Worsened |
11
91.7%
|
| Pain in arm or Shoulder: Stable |
12
100%
|
| Pain in other parts: Improved |
10
83.3%
|
| Pain in other parts: Worsened |
14
116.7%
|
| Pain in other parts: Stable |
15
125%
|
| Title | Dermatology Life Quality Index (DLQI) Total Score - Phase 2 |
|---|---|
| Description | DLQI: 10-item questionnaire to measure how much the participant's skin problem has impacted their life over the previous week. All questions were answered on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much/prevented work or studying). The DLQI was calculated by summing the score of each question and ranged from 0 to 30, where higher scores indicate more quality of life impairment. |
| Time Frame | C1D1 (baseline), D1 of each subsequent cycle up to C44 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all enrolled participants. Here "number analyzed" signifies participants who were evaluable for specified time-point for each treatment arm, respectively. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 43 |
| C1D1 |
0.81
(1.99)
|
| C2D1 |
6.54
(5.51)
|
| C3D1 |
9.51
(7.88)
|
| C4D1 |
10.85
(7.49)
|
| C5D1 |
11.04
(6.77)
|
| C6D1 |
10.76
(8.04)
|
| C7D1 |
9.47
(6.27)
|
| C8D1 |
9.92
(5.56)
|
| C9D1 |
9.58
(4.44)
|
| C10D1 |
10.22
(6.10)
|
| C11D1 |
11.25
(6.09)
|
| C12D1 |
9.00
(4.36)
|
| C13D1 |
8.71
(6.05)
|
| C14D1 |
9.80
(6.76)
|
| C15D1 |
9.60
(5.94)
|
| C16D1 |
9.25
(7.04)
|
| C17D1 |
11.50
(10.28)
|
| C18D1 |
9.00
(7.07)
|
| C19D1 |
8.75
(6.18)
|
| C20D1 |
7.00
(6.48)
|
| C21D1 |
7.00
(6.98)
|
| C22D1 |
7.75
(5.56)
|
| C23D1 |
7.75
(5.50)
|
| C24D1 |
10.00
(2.83)
|
| C25D1 |
11.00
(1.41)
|
| C26D1 |
12.00
(NA)
|
| C27D1 |
13.00
(NA)
|
| C28D1 |
12.00
(NA)
|
| C29D1 |
12.00
(NA)
|
| C30D1 |
12.00
(NA)
|
| C31D1 |
12.00
(NA)
|
| C32D1 |
12.00
(NA)
|
| C33D1 |
12.00
(NA)
|
| C34D1 |
12.00
(NA)
|
| C35D1 |
14.00
(NA)
|
| C36D1 |
12.00
(NA)
|
| C37D1 |
10.00
(NA)
|
| C38D1 |
11.00
(NA)
|
| C39D1 |
13.00
(NA)
|
| C40D1 |
12.00
(NA)
|
| C41D1 |
13.00
(NA)
|
| C42D1 |
12.00
(NA)
|
| C43D1 |
12.00
(NA)
|
| C44D1 |
12.00
(NA)
|
| Title | Best Overall Response (BOR) - Phase 2 |
|---|---|
| Description | Number of participants with BOR according to RECIST: CR= disappearance of all target and non-target lesions. PR= at least 30% decrease in sum of LDs of target lesion, taking as reference baseline sum LD, associated to non-progressive disease response for non-target lesions. Stable/no response= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Objective progression= at least a 20% increase in sum of LDs of target lesions, taking as reference the smallest sum of LD recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time Frame | Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after EOT (EOT: up to Day 1723) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population included all enrolled participants who received at least 1 dose of study medication, had an adequate baseline tumor assessment, and had at least 1 on-study tumor assessment after first dosing. |
| Arm/Group Title | PF-00299804 45 mg - Phase 2 |
|---|---|
| Arm/Group Description | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 41 |
| Complete Response |
0
0%
|
| Partial Response |
7
58.3%
|
| Stable/No Response |
21
175%
|
| Objective Progression |
13
108.3%
|
| Indeterminate |
0
0%
|
| Title | Duration of Response (DR) |
|---|---|
| Description | Time in weeks from first documentation of objective tumor response to objective tumor progression or death due to any cause, whichever occurred first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Time Frame | Baseline until disease progression or initiation of new anti-cancer therapy or death, assessed every 2 (odd-numbered) cycles up to 12 months after EOT (EOT: up to Day 506 for Phase 1 and up to Day 1723 for Phase 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included sub-set of participants from response-evaluable population, who had a confirmed objective tumor response (CR or PR). |
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 | PF-00299804 45 mg - Phase 2 |
|---|---|---|---|
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. |
| Measure Participants | 0 | 2 | 7 |
| Median (95% Confidence Interval) [weeks] |
41.9
|
60.6
|
Adverse Events
| Time Frame | Adverse events were recorded from the time that the participant provided informed consent through and including 28 calendar days after the last administration of the investigational product. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. | |||||
| Arm/Group Title | PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 | PF-00299804 45 mg - Phase 2 | |||
| Arm/Group Description | A single dose of PF-00299804 30 milligram (mg) tablet orally on or before Day -9 followed by PF-00299804 30 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | A single dose of PF-00299804 45 mg tablet orally on or before Day -9 followed by PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | PF-00299804 45 mg tablet orally once daily continuously in 21-day cycles starting from Day 1 until unacceptable toxicity, disease progression, withdrawal from the trial, or death. | |||
All Cause Mortality |
||||||
| PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 | PF-00299804 45 mg - Phase 2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 | PF-00299804 45 mg - Phase 2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 0/6 (0%) | 9/43 (20.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 0/6 (0%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 0/6 (0%) | 0/6 (0%) | 1/43 (2.3%) | |||
| General disorders | ||||||
| Disease progression | 0/6 (0%) | 0/6 (0%) | 5/43 (11.6%) | |||
| Infections and infestations | ||||||
| Pneumonia | 0/6 (0%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Nervous system disorders | ||||||
| Hydrocephalus | 0/6 (0%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pleural effusion | 1/6 (16.7%) | 0/6 (0%) | 0/43 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 0/6 (0%) | 0/6 (0%) | 1/43 (2.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| PF-00299804 30 mg - Phase 1 | PF-00299804 45 mg - Phase 1 | PF-00299804 45 mg - Phase 2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 6/6 (100%) | 41/43 (95.3%) | |||
| Ear and labyrinth disorders | ||||||
| Hearing impaired | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Abdominal pain upper | 0/6 (0%) | 0/6 (0%) | 4/43 (9.3%) | |||
| Constipation | 1/6 (16.7%) | 0/6 (0%) | 4/43 (9.3%) | |||
| Diarrhoea | 2/6 (33.3%) | 6/6 (100%) | 36/43 (83.7%) | |||
| Dry mouth | 1/6 (16.7%) | 0/6 (0%) | 0/43 (0%) | |||
| Dyspepsia | 0/6 (0%) | 0/6 (0%) | 6/43 (14%) | |||
| Nausea | 1/6 (16.7%) | 2/6 (33.3%) | 7/43 (16.3%) | |||
| Stomatitis | 2/6 (33.3%) | 3/6 (50%) | 20/43 (46.5%) | |||
| Vomiting | 0/6 (0%) | 1/6 (16.7%) | 2/43 (4.7%) | |||
| General disorders | ||||||
| Asthenia | 0/6 (0%) | 0/6 (0%) | 3/43 (7%) | |||
| Chest discomfort | 0/6 (0%) | 1/6 (16.7%) | 2/43 (4.7%) | |||
| Chest pain | 1/6 (16.7%) | 1/6 (16.7%) | 3/43 (7%) | |||
| Fatigue | 0/6 (0%) | 0/6 (0%) | 8/43 (18.6%) | |||
| Mucosal inflammation | 2/6 (33.3%) | 3/6 (50%) | 7/43 (16.3%) | |||
| Pyrexia | 0/6 (0%) | 0/6 (0%) | 3/43 (7%) | |||
| Xerosis | 0/6 (0%) | 1/6 (16.7%) | 1/43 (2.3%) | |||
| Infections and infestations | ||||||
| Gingivitis | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Folliculitis | 0/6 (0%) | 1/6 (16.7%) | 2/43 (4.7%) | |||
| Paronychia | 3/6 (50%) | 3/6 (50%) | 29/43 (67.4%) | |||
| Pneumonia | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/6 (0%) | 2/6 (33.3%) | 14/43 (32.6%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/6 (16.7%) | 0/6 (0%) | 3/43 (7%) | |||
| Back pain | 0/6 (0%) | 0/6 (0%) | 4/43 (9.3%) | |||
| Flank pain | 0/6 (0%) | 0/6 (0%) | 4/43 (9.3%) | |||
| Musculoskeletal chest pain | 0/6 (0%) | 1/6 (16.7%) | 2/43 (4.7%) | |||
| Musculoskeletal pain | 2/6 (33.3%) | 1/6 (16.7%) | 7/43 (16.3%) | |||
| Neck pain | 0/6 (0%) | 1/6 (16.7%) | 2/43 (4.7%) | |||
| Pain in extremity | 0/6 (0%) | 1/6 (16.7%) | 4/43 (9.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Tumour pain | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/6 (16.7%) | 1/6 (16.7%) | 3/43 (7%) | |||
| Headache | 1/6 (16.7%) | 1/6 (16.7%) | 1/43 (2.3%) | |||
| Hypoaesthesia | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Neuropathy peripheral | 1/6 (16.7%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 0/6 (0%) | 1/6 (16.7%) | 2/43 (4.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 3/6 (50%) | 0/6 (0%) | 9/43 (20.9%) | |||
| Dyspnoea | 1/6 (16.7%) | 2/6 (33.3%) | 7/43 (16.3%) | |||
| Dyspnoea exertional | 1/6 (16.7%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Epistaxis | 1/6 (16.7%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Haemoptysis | 2/6 (33.3%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Nasal disorder | 0/6 (0%) | 0/6 (0%) | 3/43 (7%) | |||
| Nasal inflammation | 0/6 (0%) | 0/6 (0%) | 4/43 (9.3%) | |||
| Oropharyngeal pain | 0/6 (0%) | 0/6 (0%) | 4/43 (9.3%) | |||
| Pleural effusion | 1/6 (16.7%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Productive cough | 0/6 (0%) | 0/6 (0%) | 5/43 (11.6%) | |||
| Rhinorrhoea | 1/6 (16.7%) | 0/6 (0%) | 5/43 (11.6%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis | 1/6 (16.7%) | 0/6 (0%) | 1/43 (2.3%) | |||
| Dermatitis acneiform | 4/6 (66.7%) | 6/6 (100%) | 35/43 (81.4%) | |||
| Dry skin | 0/6 (0%) | 1/6 (16.7%) | 16/43 (37.2%) | |||
| Hair disorder | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
| Palmar-plantar erythrodysaesthesia syndrome | 2/6 (33.3%) | 3/6 (50%) | 13/43 (30.2%) | |||
| Pruritus | 2/6 (33.3%) | 0/6 (0%) | 15/43 (34.9%) | |||
| Rash | 1/6 (16.7%) | 0/6 (0%) | 0/43 (0%) | |||
| Rash erythematous | 1/6 (16.7%) | 0/6 (0%) | 5/43 (11.6%) | |||
| Skin exfoliation | 1/6 (16.7%) | 0/6 (0%) | 2/43 (4.7%) | |||
| Vascular disorders | ||||||
| Lymphoedema | 0/6 (0%) | 1/6 (16.7%) | 0/43 (0%) | |||
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 less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00553254
Other Study ID Numbers:
- A7471003
First Posted:
Nov 4, 2007
Last Update Posted:
Oct 19, 2020
Last Verified:
Sep 1, 2020