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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00113529
Recruitment Status : Completed
First Posted : June 9, 2005
Results First Posted : March 31, 2010
Last Update Posted : August 29, 2011
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Renal Cell
Intervention Drug: Gefitinib + Sunitinib
Enrollment 42
Recruitment Details  
Pre-assignment Details 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
Hide 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 [1]
Completed 1 [2]
Not Completed 34
Reason Not Completed
Adverse Event             4
Lack of Efficacy             20
Decision of sponsor             6
Withdrawal by Subject             4
[1]
Phase 2 included 4 subjects from Phase 1 and 31 from Phase 2, for a total of 35 subjects.
[2]
Subject discontinued from the study and continued treatment on commercially available sunitinib.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Baseline Participants 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants
< 65 years 19
> = 65 years 16
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Female
9
  25.7%
Male
26
  74.3%
1.Primary Outcome
Title Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
13
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Objective Response Rate (ORR) (percent)
Estimated Value 37.1
Confidence Interval 95%
21.5 to 55.1
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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = those who had a confirmed response on study.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: weeks
16.0
(4.3 to 21.1)
3.Secondary Outcome
Title Duration of Response (DR)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 4
Median (Full Range)
Unit of Measure: weeks
52.2
(26.6 to 80.1)
4.Secondary Outcome
Title Time to Tumor Progression (TTP)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = those who progressed on study.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: weeks
48.4
(28.1 to 84.0)
5.Secondary Outcome
Title Overall Survival (OS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = subjects who died.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 12
Median (Full Range)
Unit of Measure: weeks
49.5
(16.1 to 93.3)
6.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 19
Median (95% Confidence Interval)
Unit of Measure: weeks
48.4
(28.1 to 84.0)
7.Secondary Outcome
Title Probability of Survival at One Year
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: probability
82.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter probability
Estimated Value 82.4
Confidence Interval 95%
64.9 to 91.7
Estimation Comments [Not Specified]
8.Secondary Outcome
Title VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline
Hide Description Concentration of VEGF at baseline.
Time Frame Baseline (Cycle 1, Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: pg/mL
63.79  (43.437)
9.Secondary Outcome
Title VEGF Ratio to Baseline at Each Time Point
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: ratio
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
Hide Description Concentration of VEGF-C at baseline.
Time Frame Baseline (Cycle 1, Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: pg/mL
725.82  (533.798)
11.Secondary Outcome
Title VEGF-C Ratio to Baseline at Each Time Point
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: ratio
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
Hide Description Concentration of sVEGFR2 at baseline.
Time Frame Baseline (Cycle 1, Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: pg/mL
10525.0  (2198.017)
13.Secondary Outcome
Title sVEGFR2 Ratio to Baseline at Each Time Point
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: ratio
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
Hide Description Concentration of sVEGFR3 at baseline.
Time Frame Baseline (Cycle 1, Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Arm/Group Title Sunitinib + Gefitinib
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: pg/mL
48355.48  (19623.342)
15.Secondary Outcome
Title sVEGFR3 Ratio to Baseline at Each Time Point
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: ratio
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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.749
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.834
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.332
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.473
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.286
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.277
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.956
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.275
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.227
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 31
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.435
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.722
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.645
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.854
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.230
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.462
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.423
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.510
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.608
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
22.Secondary Outcome
Title Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.910
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.509
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.883
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.582
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
23.Secondary Outcome
Title Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.428
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
24.Secondary Outcome
Title Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.854
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.230
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.067
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.462
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.423
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.510
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.608
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
26.Secondary Outcome
Title Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.910
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.509
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.883
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.582
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
27.Secondary Outcome
Title Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: pg/mL
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.428
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 1, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 2, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.019
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sunitinib + Gefitinib
Comments Cycle 3, Day 28
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments [Not Specified]
Method Wilcoxon Rank Sum Test
Comments [Not Specified]
28.Secondary Outcome
Title Trough Plasma Concentrations (Ctrough) of Sunitinib
Hide Description [Not Specified]
Time Frame prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 35
Mean (Standard Deviation)
Unit of Measure: ng/mL
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)
Hide Description [Not Specified]
Time Frame prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 35
Mean (Standard Deviation)
Unit of Measure: ng/mL
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
Hide Description [Not Specified]
Time Frame prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)
Hide Outcome Measure Data
Hide 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
Hide 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 Number of Participants Analyzed 35
Mean (Standard Deviation)
Unit of Measure: ng/mL
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)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sunitinib + Gefitinib
Hide 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 (%)
Total   --/-- 
Hide Serious Adverse Events
Sunitinib + Gefitinib
Affected / at Risk (%)
Total   11/35 (31.43%) 
Cardiac disorders   
Ventricular tachycardia  1  1/35 (2.86%) 
Myocardial ischaemia   1/35 (2.86%) 
Gastrointestinal disorders   
Gastrointestinal haemorrhage   2/35 (5.71%) 
Rectal haemorrhage   1/35 (2.86%) 
Hepatobiliary disorders   
Cholecystitis   1/35 (2.86%) 
Investigations   
Blood magnesium decreased   1/35 (2.86%) 
Blood calcium increased   1/35 (2.86%) 
Nervous system disorders   
Syncope   1/35 (2.86%) 
Renal and urinary disorders   
Haematuria   1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion   1/35 (2.86%) 
Epistaxis   1/35 (2.86%) 
Dyspnoea   1/35 (2.86%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (v8.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sunitinib + Gefitinib
Affected / at Risk (%)
Total   35/35 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  3/35 (8.57%) 
Neutropenia   2/35 (5.71%) 
Thrombocytopenia   3/35 (8.57%) 
Gastrointestinal disorders   
Constipation   8/35 (22.86%) 
Diarrhoea   34/35 (97.14%) 
Dyspepsia   15/35 (42.86%) 
Flatulence   2/35 (5.71%) 
Gastrooesophageal reflux disease   3/35 (8.57%) 
Haemorrhoids   2/35 (5.71%) 
Nausea   16/35 (45.71%) 
Oral pain   2/35 (5.71%) 
Rectal haemorrhage   2/35 (5.71%) 
Stomatitis   15/35 (42.86%) 
Vomiting   10/35 (28.57%) 
General disorders   
Fatigue   30/35 (85.71%) 
Oedema peripheral   7/35 (20.00%) 
Pyrexia   4/35 (11.43%) 
Infections and infestations   
Sinusitis   2/35 (5.71%) 
Upper respiratory tract infection   3/35 (8.57%) 
Urinary tract infection   3/35 (8.57%) 
Investigations   
Alanine aminotransferase increased   3/35 (8.57%) 
Aspartate aminotransferase increased   2/35 (5.71%) 
Blood phosphorus decreased   2/35 (5.71%) 
Blood pressure increased   3/35 (8.57%) 
Ejection fraction decreased   2/35 (5.71%) 
Weight decreased   3/35 (8.57%) 
White blood cell count decreased   4/35 (11.43%) 
Metabolism and nutrition disorders   
Anorexia   8/35 (22.86%) 
Decreased appetite   5/35 (14.29%) 
Hyperglycaemia   2/35 (5.71%) 
Hypophosphataemia   2/35 (5.71%) 
Musculoskeletal and connective tissue disorders   
Back pain   2/35 (5.71%) 
Flank pain   3/35 (8.57%) 
Muscular weakness   2/35 (5.71%) 
Pain in extremity   5/35 (14.29%) 
Nervous system disorders   
Dizziness   2/35 (5.71%) 
Dysgeusia   12/35 (34.29%) 
Headache   4/35 (11.43%) 
Hypoaesthesia   3/35 (8.57%) 
Neuropathy   2/35 (5.71%) 
Paraesthesia   3/35 (8.57%) 
Peripheral sensory neuropathy   3/35 (8.57%) 
Syncope   2/35 (5.71%) 
Renal and urinary disorders   
Dysuria   2/35 (5.71%) 
Nocturia   2/35 (5.71%) 
Pollakiuria   3/35 (8.57%) 
Respiratory, thoracic and mediastinal disorders   
Cough   6/35 (17.14%) 
Dysphonia   2/35 (5.71%) 
Dyspnoea   2/35 (5.71%) 
Dyspnoea exertional   10/35 (28.57%) 
Epistaxis   8/35 (22.86%) 
Wheezing   2/35 (5.71%) 
Skin and subcutaneous tissue disorders   
Acne   4/35 (11.43%) 
Alopecia   4/35 (11.43%) 
Blister   3/35 (8.57%) 
Dermatitis acneiform   5/35 (14.29%) 
Dry skin   12/35 (34.29%) 
Erythema   4/35 (11.43%) 
Hyperkeratosis   2/35 (5.71%) 
Night sweats   2/35 (5.71%) 
Palmar—plantar erythrodysaesthesia syndrome   11/35 (31.43%) 
Rash   20/35 (57.14%) 
Skin exfoliation   3/35 (8.57%) 
Skin lesion   2/35 (5.71%) 
Vascular disorders   
Hypertension   5/35 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (v8.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.govCallCenter@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00113529    
Other Study ID Numbers: A6181038
First Submitted: June 8, 2005
First Posted: June 9, 2005
Results First Submitted: March 1, 2010
Results First Posted: March 31, 2010
Last Update Posted: August 29, 2011