Trial Outcomes & Findings for Study Of SU011248 Plus Gefitinib (Iressa) In Patients With Advanced Renal Cell Carcinoma (NCT NCT00113529)
NCT ID: NCT00113529
Last Updated: 2011-08-29
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
42 participants
Primary outcome timeframe
From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter
Results posted on
2011-08-29
Participant Flow
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.
Participant milestones
| Measure |
Sunitinib + Gefitinib
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.
|
|---|---|
|
Overall Study
STARTED
|
35
|
|
Overall Study
COMPLETED
|
1
|
|
Overall Study
NOT COMPLETED
|
34
|
Reasons for withdrawal
| Measure |
Sunitinib + Gefitinib
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.
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Lack of Efficacy
|
20
|
|
Overall Study
Decision of sponsor
|
6
|
|
Overall Study
Withdrawal by Subject
|
4
|
Baseline Characteristics
Study Of SU011248 Plus Gefitinib (Iressa) In Patients With Advanced Renal Cell Carcinoma
Baseline characteristics by cohort
| Measure |
Sunitinib + Gefitinib
n=35 Participants
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.
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|---|---|
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Age, Customized
< 65 years
|
19 participants
n=5 Participants
|
|
Age, Customized
> = 65 years
|
16 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafterPopulation: Intent-to-treat (ITT) = all subjects enrolled in the study that received at least 1 dose of study medication (sunitinib or gefitinib).
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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=35 Participants
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.
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|---|---|
|
Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
|
13 participants
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafterPopulation: ITT. Number of participants analyzed = those who had a confirmed response on study.
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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=13 Participants
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.
|
|---|---|
|
Time to Tumor Response (TTR)
|
16.0 weeks
Interval 4.3 to 21.1
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death due to cancerPopulation: ITT. Number of participants analyzed = those who had a response and subsequent progression or death due to any cause while on study.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=4 Participants
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.
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|---|---|
|
Duration of Response (DR)
|
52.2 weeks
Interval 26.6 to 80.1
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafterPopulation: ITT. Number of participants analyzed = those who progressed on study.
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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=19 Participants
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.
|
|---|---|
|
Time to Tumor Progression (TTP)
|
48.4 weeks
Interval 28.1 to 84.0
|
SECONDARY outcome
Timeframe: From start of study treatment until deathPopulation: ITT. Number of participants analyzed = subjects who died.
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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=12 Participants
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 Survival (OS)
|
49.5 weeks
Interval 16.1 to 93.3
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or deathPopulation: ITT. Number of participants analyzed = those who progressed or died due to any cause while on study.
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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=19 Participants
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.
|
|---|---|
|
Progression-Free Survival (PFS)
|
48.4 weeks
Interval 28.1 to 84.0
|
SECONDARY outcome
Timeframe: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 yearPopulation: ITT
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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=35 Participants
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.
|
|---|---|
|
Probability of Survival at One Year
|
82.4 probability
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1)Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Concentration of VEGF at baseline.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline
|
63.79 pg/mL
Standard Deviation 43.437
|
SECONDARY outcome
Timeframe: Baseline to Cycle 3, Day 28 inclusivePopulation: 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.
VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
VEGF Ratio to Baseline at Each Time Point
Cycle 1, Day 28 (n=29)
|
2.29 ratio
Standard Deviation 1.269
|
|
VEGF Ratio to Baseline at Each Time Point
Cycle 2, Day 1 (n=26)
|
1.65 ratio
Standard Deviation 1.951
|
|
VEGF Ratio to Baseline at Each Time Point
Cycle 2, Day 28 (n=23)
|
2.65 ratio
Standard Deviation 1.956
|
|
VEGF Ratio to Baseline at Each Time Point
Cycle 3, Day 1 (n=22)
|
1.93 ratio
Standard Deviation 1.872
|
|
VEGF Ratio to Baseline at Each Time Point
Cycle 3, Day 28 (n=20)
|
2.26 ratio
Standard Deviation 1.195
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1)Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Concentration of VEGF-C at baseline.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
VEGF-C Concentration at Baseline
|
725.82 pg/mL
Standard Deviation 533.798
|
SECONDARY outcome
Timeframe: Baseline to Cycle 3, Day 28 inclusivePopulation: 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.
VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
VEGF-C Ratio to Baseline at Each Time Point
Cycle 1, Day 28 (n=29)
|
0.93 ratio
Standard Deviation 0.433
|
|
VEGF-C Ratio to Baseline at Each Time Point
Cycle 2, Day 1 (n=26)
|
0.86 ratio
Standard Deviation 0.315
|
|
VEGF-C Ratio to Baseline at Each Time Point
Cycle 2, Day 28 (n=23)
|
1.01 ratio
Standard Deviation 0.585
|
|
VEGF-C Ratio to Baseline at Each Time Point
Cycle 3, Day 1 (n=22)
|
1.09 ratio
Standard Deviation 0.573
|
|
VEGF-C Ratio to Baseline at Each Time Point
Cycle 3, Day 28 (n=20)
|
0.93 ratio
Standard Deviation 0.452
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1)Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Concentration of sVEGFR2 at baseline.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline
|
10525.0 pg/mL
Standard Deviation 2198.017
|
SECONDARY outcome
Timeframe: Baseline to Cycle 3, Day 28 inclusivePopulation: 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.
sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
sVEGFR2 Ratio to Baseline at Each Time Point
Cycle 1, Day 28 (n=29)
|
0.64 ratio
Standard Deviation 0.130
|
|
sVEGFR2 Ratio to Baseline at Each Time Point
Cycle 2, Day 1 (n=26)
|
0.82 ratio
Standard Deviation 0.181
|
|
sVEGFR2 Ratio to Baseline at Each Time Point
Cycle 2, Day 28 (n=23)
|
0.63 ratio
Standard Deviation 0.151
|
|
sVEGFR2 Ratio to Baseline at Each Time Point
Cycle 3, Day 1 (n=22)
|
0.75 ratio
Standard Deviation 0.154
|
|
sVEGFR2 Ratio to Baseline at Each Time Point
Cycle 3, Day 28 (n=20)
|
0.64 ratio
Standard Deviation 0.217
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1)Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
Concentration of sVEGFR3 at baseline.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline
|
48355.48 pg/mL
Standard Deviation 19623.342
|
SECONDARY outcome
Timeframe: Baseline to Cycle 3, Day 28 inclusivePopulation: 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.
sVEGFR3 concentration at each time point divided by sVEGFR3 concentration at baseline (ratio to baseline).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
sVEGFR3 Ratio to Baseline at Each Time Point
Cycle 1, Day 28 (n=29)
|
0.41 ratio
Standard Deviation 0.185
|
|
sVEGFR3 Ratio to Baseline at Each Time Point
Cycle 2, Day 1 (n=26)
|
0.96 ratio
Standard Deviation 0.506
|
|
sVEGFR3 Ratio to Baseline at Each Time Point
Cycle 2, Day 28 (n=23)
|
0.52 ratio
Standard Deviation 0.413
|
|
sVEGFR3 Ratio to Baseline at Each Time Point
Cycle 3, Day 1 (n=22)
|
0.89 ratio
Standard Deviation 0.453
|
|
sVEGFR3 Ratio to Baseline at Each Time Point
Cycle 3, Day 28 (n=20)
|
0.38 ratio
Standard Deviation 0.211
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (CR or PR or SD, n=22)
|
40.70 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (PD, n=5)
|
94.50 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (CR or PR or SD, n=22)
|
2.31 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (PD, n=4)
|
1.94 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (CR or PR or SD, n=22)
|
1.05 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (PD, n=3)
|
1.01 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (CR or PR or SD, n=21)
|
2.26 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (PD, n=2)
|
2.30 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1 (CR or PR or SD, n=20)
|
1.33 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1(PD, n=2)
|
0.91 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 28 (CR or PR or SD, n=20)
|
1.87 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (CR or PR or SD, n=22)
|
561.20 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (PD, n=5)
|
751.30 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (CR or PR or SD, n=22)
|
0.95 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (PD, n=4)
|
0.71 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (CR or PR or SD, n=22)
|
0.90 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (PD, n=3)
|
0.80 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (CR or PR or SD, n=21)
|
0.84 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (PD, n=2)
|
1.19 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1 (CR or PR or SD, n=20)
|
1.04 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1(PD, n=2)
|
0.69 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 28 (CR or PR or SD, n=20)
|
0.93 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (CR or PR or SD, n=22)
|
10041.50 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (PD, n=5)
|
9760.00 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (CR or PR or SD, n=22)
|
0.59 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (PD, n=4)
|
0.68 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (CR or PR or SD, n=22)
|
0.79 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (PD, n=3)
|
0.69 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (CR or PR or SD, n=21)
|
0.62 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (PD, n=2)
|
0.62 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1 (CR or PR or SD, n=20)
|
0.74 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1(PD, n=2)
|
0.73 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 28 (CR or PR or SD, n=20)
|
0.59 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=31 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (CR or PR or SD, n=22)
|
43325.00 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 1 (PD, n=5)
|
57300.00 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (CR or PR or SD, n=22)
|
0.41 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 1, Day 28 (PD, n=4)
|
0.34 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (CR or PR or SD, n=22)
|
0.87 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 1 (PD, n=3)
|
0.71 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (CR or PR or SD, n=21)
|
0.41 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 2, Day 28 (PD, n=2)
|
1.32 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1 (CR or PR or SD, n=20)
|
0.85 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 1(PD, n=2)
|
1.84 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
Cycle 3, Day 28 (CR or PR or SD, n=20)
|
0.37 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS >= Median, n=5)
|
59.30 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS < Median, n=11)
|
44.70 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS >= Median, n=5)
|
2.32 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS < Median, n=10)
|
2.28 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS >= Median, n=5)
|
0.75 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS < Median, n=9)
|
1.06 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS >= Median, n=5)
|
1.91 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS < Median, n=8)
|
2.66 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS >= Median, n=5)
|
1.04 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS < Median, n=8)
|
1.60 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS >= Median, n=5)
|
1.79 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS < Median, n=6)
|
2.31 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS >= Median, n=5)
|
650.80 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS < Median, n=11)
|
532.70 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS >= Median, n=5)
|
0.76 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS < Median, n=10)
|
0.99 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS >= Median, n=5)
|
0.80 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS < Median, n=9)
|
1.00 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS >= Median, n=5)
|
0.84 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS < Median, n=8)
|
1.17 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS >= Median, n=5)
|
0.70 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS < Median, n=8)
|
1.05 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS >= Median, n=5)
|
0.90 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS < Median, n=6)
|
1.22 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS >= Median, n=5)
|
9100.00 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS < Median, n=11)
|
10145.00 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS >= Median, n=5)
|
0.56 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS < Median, n=10)
|
0.69 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS >= Median, n=5)
|
0.79 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS < Median, n=9)
|
0.78 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS >= Median, n=5)
|
0.56 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS < Median, n=8)
|
0.64 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS >= Median, n=5)
|
0.74 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS < Median, n=8)
|
0.75 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS >= Median, n=5)
|
0.52 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS < Median, n=6)
|
0.62 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS >= Median, n=5)
|
55100.00 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 1 (PFS < Median, n=11)
|
47500.00 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS >= Median, n=5)
|
0.29 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 1, Day 28 (PFS < Median, n=10)
|
0.44 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS >= Median, n=5)
|
0.86 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 1 (PFS < Median, n=9)
|
0.73 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS >= Median, n=5)
|
0.30 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 2, Day 28 (PFS < Median, n=8)
|
0.47 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS >= Median, n=5)
|
0.65 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 1 (PFS < Median, n=8)
|
0.91 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS >= Median, n=5)
|
0.32 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
Cycle 3, Day 28 (PFS < Median, n=6)
|
0.49 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP >= Median, n=5)
|
59.30 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP < Median, n=11)
|
44.70 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP >= Median, n=5)
|
2.32 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP < Median, n=10)
|
2.28 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP >= Median, n=5)
|
0.75 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP < Median, n=9)
|
1.06 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP >= Median, n=5)
|
1.91 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP < Median, n=8)
|
2.66 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP >= Median, n=5)
|
1.04 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP < Median, n=8)
|
1.60 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP >= Median, n=5)
|
1.79 pg/mL
|
|
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP < Median, n=6)
|
2.31 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP >= Median, n=5)
|
650.80 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP < Median, n=11)
|
532.70 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP >= Median, n=5)
|
0.76 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP < Median, n=10)
|
0.99 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP >= Median, n=5)
|
0.80 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP < Median, n=9)
|
1.00 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP >= Median, n=5)
|
0.84 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP < Median, n=8)
|
1.17 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP >= Median, n=5)
|
0.70 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP < Median, n=8)
|
1.05 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP >= Median, n=5)
|
0.90 pg/mL
|
|
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP < Median, n=6)
|
1.22 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP >= Median, n=5)
|
9100.00 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP < Median, n=11)
|
10145.00 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP >= Median, n=5)
|
0.56 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP < Median, n=10)
|
0.69 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP >= Median, n=5)
|
0.79 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP < Median, n=9)
|
0.78 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP >= Median, n=5)
|
0.56 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP < Median, n=8)
|
0.64 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP >= Median, n=5)
|
0.74 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP < Median, n=8)
|
0.75 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP >= Median, n=5)
|
0.52 pg/mL
|
|
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP < Median, n=6)
|
0.62 pg/mL
|
SECONDARY outcome
Timeframe: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusivePopulation: 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.
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).
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=16 Participants
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.
|
|---|---|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP >= Median, n=5)
|
55100.00 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 1 (TTP < Median, n=11)
|
47500.00 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP >= Median, n=5)
|
0.29 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 1, Day 28 (TTP < Median, n=10)
|
0.44 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP >= Median, n=5)
|
0.86 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 1 (TTP < Median, n=9)
|
0.73 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP >= Median, n=5)
|
0.30 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 2, Day 28 (TTP < Median, n=8)
|
0.47 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP >= Median, n=5)
|
0.65 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 1 (TTP < Median, n=8)
|
0.91 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP >= Median, n=5)
|
0.32 pg/mL
|
|
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
Cycle 3, Day 28 (TTP < Median, n=6)
|
0.49 pg/mL
|
SECONDARY outcome
Timeframe: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)Population: 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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=35 Participants
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.
|
|---|---|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 1, Day 1 (n=35)
|
1.57 ng/mL
Standard Deviation 9.263
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 1, Day 28 (n=33)
|
33.16 ng/mL
Standard Deviation 13.915
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 2, Day 1 (n=28)
|
3.25 ng/mL
Standard Deviation 3.209
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 2, Day 28 (n=27)
|
35.50 ng/mL
Standard Deviation 11.957
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 3, Day 1 (n=25)
|
3.71 ng/mL
Standard Deviation 3.335
|
|
Trough Plasma Concentrations (Ctrough) of Sunitinib
Cycle 3, Day 28 (n=24)
|
35.97 ng/mL
Standard Deviation 12.462
|
SECONDARY outcome
Timeframe: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)Population: 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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=35 Participants
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.
|
|---|---|
|
Ctrough of SU-012662 (Sunitinib's Metabolite)
Cycle 1, Day 1 (n=35)
|
1.16 ng/mL
Standard Deviation 6.846
|
|
Ctrough of SU-012662 (Sunitinib's Metabolite)
Cycle 1, Day 28 (n=33)
|
16.21 ng/mL
Standard Deviation 9.381
|
|
Ctrough of SU-012662 (Sunitinib's Metabolite)
Cycle 2, Day 1 (n=28)
|
3.03 ng/mL
Standard Deviation 2.227
|
|
Ctrough of SU-012662 (Sunitinib's Metabolite)
Cycle 2, Day 28 (n=27)
|
15.25 ng/mL
Standard Deviation 6.310
|
|
Ctrough of SU-012662 (Sunitinib's Metabolite)
Cycle 3, Day 1 (n=25)
|
3.18 ng/mL
Standard Deviation 3.564
|
|
Ctrough of SU-012662 (Sunitinib's Metabolite)
Cycle 3, Day 28 (n=24)
|
14.56 ng/mL
Standard Deviation 8.019
|
SECONDARY outcome
Timeframe: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)Population: 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.
Outcome measures
| Measure |
Sunitinib + Gefitinib
n=35 Participants
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.
|
|---|---|
|
Ctrough of Gefitinib
Cycle 1, Day 1 (n=35)
|
0.00 ng/mL
Standard Deviation 0.000
|
|
Ctrough of Gefitinib
Cycle 1, Day 28 (n=33)
|
254.74 ng/mL
Standard Deviation 191.631
|
|
Ctrough of Gefitinib
Cycle 2, Day 1 (n=24)
|
328.91 ng/mL
Standard Deviation 280.286
|
|
Ctrough of Gefitinib
Cycle 2, Day 28 (n=27)
|
263.23 ng/mL
Standard Deviation 210.287
|
|
Ctrough of Gefitinib
Cycle 3, Day 1 (n=26)
|
293.14 ng/mL
Standard Deviation 277.288
|
|
Ctrough of Gefitinib
Cycle 3, Day 28 (n=24)
|
211.43 ng/mL
Standard Deviation 102.670
|
Adverse Events
Sunitinib + Gefitinib
Serious events: 11 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sunitinib + Gefitinib
n=35 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Ventricular tachycardia
|
2.9%
1/35
|
|
Cardiac disorders
Myocardial ischaemia
|
2.9%
1/35
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
5.7%
2/35
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
2.9%
1/35
|
|
Hepatobiliary disorders
Cholecystitis
|
2.9%
1/35
|
|
Investigations
Blood magnesium decreased
|
2.9%
1/35
|
|
Investigations
Blood calcium increased
|
2.9%
1/35
|
|
Nervous system disorders
Syncope
|
2.9%
1/35
|
|
Renal and urinary disorders
Haematuria
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.9%
1/35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.9%
1/35
|
Other adverse events
| Measure |
Sunitinib + Gefitinib
n=35 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.6%
3/35
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.7%
2/35
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
8.6%
3/35
|
|
Gastrointestinal disorders
Constipation
|
22.9%
8/35
|
|
Gastrointestinal disorders
Diarrhoea
|
97.1%
34/35
|
|
Gastrointestinal disorders
Dyspepsia
|
42.9%
15/35
|
|
Gastrointestinal disorders
Flatulence
|
5.7%
2/35
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
8.6%
3/35
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.7%
2/35
|
|
Gastrointestinal disorders
Nausea
|
45.7%
16/35
|
|
Gastrointestinal disorders
Oral pain
|
5.7%
2/35
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
5.7%
2/35
|
|
Gastrointestinal disorders
Stomatitis
|
42.9%
15/35
|
|
Gastrointestinal disorders
Vomiting
|
28.6%
10/35
|
|
General disorders
Fatigue
|
85.7%
30/35
|
|
General disorders
Oedema peripheral
|
20.0%
7/35
|
|
General disorders
Pyrexia
|
11.4%
4/35
|
|
Infections and infestations
Sinusitis
|
5.7%
2/35
|
|
Infections and infestations
Upper respiratory tract infection
|
8.6%
3/35
|
|
Infections and infestations
Urinary tract infection
|
8.6%
3/35
|
|
Investigations
Alanine aminotransferase increased
|
8.6%
3/35
|
|
Investigations
Aspartate aminotransferase increased
|
5.7%
2/35
|
|
Investigations
Blood phosphorus decreased
|
5.7%
2/35
|
|
Investigations
Blood pressure increased
|
8.6%
3/35
|
|
Investigations
Ejection fraction decreased
|
5.7%
2/35
|
|
Investigations
Weight decreased
|
8.6%
3/35
|
|
Investigations
White blood cell count decreased
|
11.4%
4/35
|
|
Metabolism and nutrition disorders
Anorexia
|
22.9%
8/35
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.3%
5/35
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.7%
2/35
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.7%
2/35
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
2/35
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
8.6%
3/35
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.7%
2/35
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
5/35
|
|
Nervous system disorders
Dizziness
|
5.7%
2/35
|
|
Nervous system disorders
Dysgeusia
|
34.3%
12/35
|
|
Nervous system disorders
Headache
|
11.4%
4/35
|
|
Nervous system disorders
Hypoaesthesia
|
8.6%
3/35
|
|
Nervous system disorders
Neuropathy
|
5.7%
2/35
|
|
Nervous system disorders
Paraesthesia
|
8.6%
3/35
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
8.6%
3/35
|
|
Nervous system disorders
Syncope
|
5.7%
2/35
|
|
Renal and urinary disorders
Dysuria
|
5.7%
2/35
|
|
Renal and urinary disorders
Nocturia
|
5.7%
2/35
|
|
Renal and urinary disorders
Pollakiuria
|
8.6%
3/35
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.1%
6/35
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.7%
2/35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
28.6%
10/35
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
22.9%
8/35
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
Acne
|
11.4%
4/35
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
11.4%
4/35
|
|
Skin and subcutaneous tissue disorders
Blister
|
8.6%
3/35
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
14.3%
5/35
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
34.3%
12/35
|
|
Skin and subcutaneous tissue disorders
Erythema
|
11.4%
4/35
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.7%
2/35
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
31.4%
11/35
|
|
Skin and subcutaneous tissue disorders
Rash
|
57.1%
20/35
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
8.6%
3/35
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
5.7%
2/35
|
|
Vascular disorders
Hypertension
|
14.3%
5/35
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER