Carcinoma, Renal Cell
Conditions
Brief summary
To assess the maximum tolerated dose and overall safety and tolerability of sunitinib \[SU011248\] administered in combination with gefitinib (Iressa) for the treatment of patients with metastatic renal cell carcinoma (Phase 1). To assess antitumor activity of the combination of gefitinib and sunitinib (Phase 2).
Interventions
DRUGGefitinib + Sunitinib
Until disease progression or unacceptable toxicity.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed renal cell carcinoma with metastases * Evidence of unidimensionally measurable disease * Failure of 1 prior immunotherapy or no prior systemic therapy for metastatic RCC
Exclusion criteria
* RCC without any clear (conventional) cell component * History of or known brain metastases * Uncontrolled hypertension or other significant cardiac events within the 12 months prior to study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) | From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter | Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DR) | From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death due to cancer | DR was defined as the time from start of the first documentation of objective tumor response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as (the end date for DR minus first CR or PR that was subsequently confirmed +1)/7. DR was calculated for the subgroup of subjects with an objective tumor response (CR or PR). |
| Time to Tumor Progression (TTP) | From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter | TTP was defined as the time from the date of first dose of study medication to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used. |
| Overall Survival (OS) | From start of study treatment until death | OS was defined as the time from date of the first dose of study medication to date of death due to any cause. OS (in weeks) is calculated as (date of death minus first dose date +1)/7. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose had their survival times censored at 1 day. Kaplan-Meier method was used. |
| Progression-Free Survival (PFS) | From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death | PFS was defined as the time from the date of first dose of study medication to the date of first documentation of tumor progression or death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used. |
| Probability of Survival at One Year | From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year | Survival rate was defined as the percentage of subjects alive at 1 year after the date of first administration of study medication. Survival rate was estimated using the Kaplan-Meier method. |
| VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline | Baseline (Cycle 1, Day 1) | Concentration of VEGF at baseline. |
| VEGF Ratio to Baseline at Each Time Point | Baseline to Cycle 3, Day 28 inclusive | VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline). |
| VEGF-C Concentration at Baseline | Baseline (Cycle 1, Day 1) | Concentration of VEGF-C at baseline. |
| VEGF-C Ratio to Baseline at Each Time Point | Baseline to Cycle 3, Day 28 inclusive | VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline). |
| Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline | Baseline (Cycle 1, Day 1) | Concentration of sVEGFR2 at baseline. |
| sVEGFR2 Ratio to Baseline at Each Time Point | Baseline to Cycle 3, Day 28 inclusive | sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline). |
| Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline | Baseline (Cycle 1, Day 1) | Concentration of sVEGFR3 at baseline. |
| sVEGFR3 Ratio to Baseline at Each Time Point | Baseline to Cycle 3, Day 28 inclusive | sVEGFR3 concentration at each time point divided by sVEGFR3 concentration at baseline (ratio to baseline). |
| Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGF level at each specified time point for subjects with tumor response (CR or PR or \[SD \> = 6 weeks\] versus PD) minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Time to Tumor Response (TTR) | From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter | TTR was defined as the time from date of the first dose of study medication to first documentation of objective tumor response (CR or PR). For subjects proceeding from PR to CR, the onset of PR was taken as the onset of response. If lesion assessment data included more than 1 date, the first date was used. TTR was calculated as (first event date minus first dose date +1)/7. TTR was calculated based on the subgroup of subjects with a baseline disease assessment, who had the correct histological cancer type, and had a confirmed objective tumor response. Kaplan-Meier method was used. |
| Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFR2 level at each specified time point for subjects with tumor response (CR or PR or \[SD \> = 6 weeks\] versus PD) minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFR3 level at each specified time point for subjects with tumor response (CR or PR or \[SD \> = 6 weeks\] versus PD) minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGF level at each specified time point for subjects with tumor response PFS \>= Median or PFS \< Median minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFC level at each specified time point for subjects with tumor response PFS \>= Median or PFS \< Median minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFR2 level at each specified time point for subjects with tumor response PFS \>= Median or PFS \< Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFR3 level at each specified time point for subjects with tumor response PFS \>= Median or PFS \< Median minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGF level at each specified time point for subjects with tumor response TTP \>= Median and TTP \< Median minus median VEGF level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFC level at each specified time point for subjects with tumor response TTP \>= Median and TTP \< Median minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFR2 level at each specified time point for subjects with tumor response TTP \>= Median and TTP \< Median minus median VEGFR2 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFR3 level at each specified time point for subjects with tumor response TTP \>= Median and TTP \< Median minus median VEGFR3 level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
| Trough Plasma Concentrations (Ctrough) of Sunitinib | prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) | — |
| Ctrough of SU-012662 (Sunitinib's Metabolite) | prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) | — |
| Ctrough of Gefitinib | prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) | — |
| Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) | Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive | Change = median VEGFC level at each specified time point for subjects with tumor response (CR or PR or \[SD \> = 6 weeks\] versus PD) minus median VEGFC level at Baseline. A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib + Gefitinib 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. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Decision of sponsor | 6 |
| Overall Study | Lack of Efficacy | 20 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Sunitinib + Gefitinib |
|---|---|
| Age, Customized < 65 years | 19 participants |
| Age, Customized > = 65 years | 16 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 11 / 35 |
Outcome results
Primary
Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
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
Population: Intent-to-treat (ITT) = all subjects enrolled in the study that received at least 1 dose of study medication (sunitinib or gefitinib).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib + Gefitinib | Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) | 13 participants |
95% CI: [21.5, 55.1]
Secondary
Change From Baseline in VEGF by Time Point Stratified by PFS >= Median and PFS < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.734Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.854Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.23Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.067Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.164Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.121Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGF by Time Point Stratified by TTP >= Median and TTP < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.734Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.854Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.23Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.067Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.164Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.121Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGF by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.075Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.749Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.834Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 1Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.332Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFC by Time Point Stratified by PFS >= Median and PFS < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.734Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.462Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.423Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.51Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.608Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.121Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFC by Time Point Stratified by TTP >= Median and TTP < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.734Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.462Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.423Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.51Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.608Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.121Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.473Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.286Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.277Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.956Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.278Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFR2 by Time Point Stratified by PFS >= Median and PFS < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.91Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.02Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 1Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.509Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.883Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.582Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFR2 by Time Point Stratified by TTP >= Median and TTP < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.91Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.02Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 1Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.509Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.883Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.582Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.275Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.227Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.029Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 1Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 1Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFR3 by Time Point Stratified by PFS >= Median and PFS < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.428Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.075Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 1Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.019Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.124Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.055Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFR3 by Time Point Stratified by TTP >= Median and TTP < Median
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.428Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.075Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 1Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.019Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.124Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 28p-value: 0.055Wilcoxon Rank Sum Test
Secondary
Change From Baseline in VEGFR3 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
| Sunitinib + Gefitinib | 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 |
Comparison: Cycle 1, Day 1p-value: 0.435Wilcoxon Rank Sum Test
Comparison: Cycle 1, Day 28p-value: 0.722Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 1p-value: 0.645Wilcoxon Rank Sum Test
Comparison: Cycle 2, Day 28p-value: 0.14Wilcoxon Rank Sum Test
Comparison: Cycle 3, Day 1p-value: 0.046Wilcoxon Rank Sum Test
Secondary
Ctrough of Gefitinib
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | Ctrough of Gefitinib | Cycle 1, Day 1 (n=35) | 0.00 ng/mL | Standard Deviation 0 |
| Sunitinib + Gefitinib | Ctrough of Gefitinib | Cycle 1, Day 28 (n=33) | 254.74 ng/mL | Standard Deviation 191.631 |
| Sunitinib + Gefitinib | Ctrough of Gefitinib | Cycle 2, Day 1 (n=24) | 328.91 ng/mL | Standard Deviation 280.286 |
| Sunitinib + Gefitinib | Ctrough of Gefitinib | Cycle 2, Day 28 (n=27) | 263.23 ng/mL | Standard Deviation 210.287 |
| Sunitinib + Gefitinib | Ctrough of Gefitinib | Cycle 3, Day 1 (n=26) | 293.14 ng/mL | Standard Deviation 277.288 |
| Sunitinib + Gefitinib | Ctrough of Gefitinib | Cycle 3, Day 28 (n=24) | 211.43 ng/mL | Standard Deviation 102.67 |
Secondary
Ctrough of SU-012662 (Sunitinib's Metabolite)
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | Ctrough of SU-012662 (Sunitinib's Metabolite) | Cycle 2, Day 28 (n=27) | 15.25 ng/mL | Standard Deviation 6.31 |
| Sunitinib + Gefitinib | Ctrough of SU-012662 (Sunitinib's Metabolite) | Cycle 1, Day 1 (n=35) | 1.16 ng/mL | Standard Deviation 6.846 |
| Sunitinib + Gefitinib | Ctrough of SU-012662 (Sunitinib's Metabolite) | Cycle 1, Day 28 (n=33) | 16.21 ng/mL | Standard Deviation 9.381 |
| Sunitinib + Gefitinib | Ctrough of SU-012662 (Sunitinib's Metabolite) | Cycle 2, Day 1 (n=28) | 3.03 ng/mL | Standard Deviation 2.227 |
| Sunitinib + Gefitinib | Ctrough of SU-012662 (Sunitinib's Metabolite) | Cycle 3, Day 1 (n=25) | 3.18 ng/mL | Standard Deviation 3.564 |
| Sunitinib + Gefitinib | Ctrough of SU-012662 (Sunitinib's Metabolite) | Cycle 3, Day 28 (n=24) | 14.56 ng/mL | Standard Deviation 8.019 |
Secondary
Duration of Response (DR)
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
Population: ITT. Number of participants analyzed = those who had a response and subsequent progression or death due to any cause while on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib + Gefitinib | Duration of Response (DR) | 52.2 weeks |
Secondary
Overall Survival (OS)
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
Population: ITT. Number of participants analyzed = subjects who died.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib + Gefitinib | Overall Survival (OS) | 49.5 weeks |
Secondary
Probability of Survival at One Year
Survival rate was defined as the percentage of subjects alive at 1 year after the date of first administration of study medication. Survival rate was estimated using the Kaplan-Meier method.
Time frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib + Gefitinib | Probability of Survival at One Year | 82.4 probability |
95% CI: [64.9, 91.7]
Secondary
Progression-Free Survival (PFS)
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
Population: ITT. Number of participants analyzed = those who progressed or died due to any cause while on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib + Gefitinib | Progression-Free Survival (PFS) | 48.4 weeks |
Secondary
Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline
Concentration of sVEGFR2 at baseline.
Time frame: Baseline (Cycle 1, Day 1)
Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib + Gefitinib | Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline | 10525.0 pg/mL | Standard Deviation 2198.017 |
Secondary
Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline
Concentration of sVEGFR3 at baseline.
Time frame: Baseline (Cycle 1, Day 1)
Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib + Gefitinib | Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline | 48355.48 pg/mL | Standard Deviation 19623.342 |
Secondary
sVEGFR2 Ratio to Baseline at Each Time Point
sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).
Time frame: Baseline to Cycle 3, Day 28 inclusive
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | sVEGFR2 Ratio to Baseline at Each Time Point | Cycle 1, Day 28 (n=29) | 0.64 ratio | Standard Deviation 0.13 |
| Sunitinib + Gefitinib | sVEGFR2 Ratio to Baseline at Each Time Point | Cycle 2, Day 1 (n=26) | 0.82 ratio | Standard Deviation 0.181 |
| Sunitinib + Gefitinib | sVEGFR2 Ratio to Baseline at Each Time Point | Cycle 2, Day 28 (n=23) | 0.63 ratio | Standard Deviation 0.151 |
| Sunitinib + Gefitinib | sVEGFR2 Ratio to Baseline at Each Time Point | Cycle 3, Day 1 (n=22) | 0.75 ratio | Standard Deviation 0.154 |
| Sunitinib + Gefitinib | sVEGFR2 Ratio to Baseline at Each Time Point | Cycle 3, Day 28 (n=20) | 0.64 ratio | Standard Deviation 0.217 |
Secondary
sVEGFR3 Ratio to Baseline at Each Time Point
sVEGFR3 concentration at each time point divided by sVEGFR3 concentration at baseline (ratio to baseline).
Time frame: Baseline to Cycle 3, Day 28 inclusive
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | sVEGFR3 Ratio to Baseline at Each Time Point | Cycle 1, Day 28 (n=29) | 0.41 ratio | Standard Deviation 0.185 |
| Sunitinib + Gefitinib | sVEGFR3 Ratio to Baseline at Each Time Point | Cycle 2, Day 1 (n=26) | 0.96 ratio | Standard Deviation 0.506 |
| Sunitinib + Gefitinib | sVEGFR3 Ratio to Baseline at Each Time Point | Cycle 2, Day 28 (n=23) | 0.52 ratio | Standard Deviation 0.413 |
| Sunitinib + Gefitinib | sVEGFR3 Ratio to Baseline at Each Time Point | Cycle 3, Day 1 (n=22) | 0.89 ratio | Standard Deviation 0.453 |
| Sunitinib + Gefitinib | sVEGFR3 Ratio to Baseline at Each Time Point | Cycle 3, Day 28 (n=20) | 0.38 ratio | Standard Deviation 0.211 |
Secondary
Time to Tumor Progression (TTP)
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
Population: ITT. Number of participants analyzed = those who progressed on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib + Gefitinib | Time to Tumor Progression (TTP) | 48.4 weeks |
Secondary
Time to Tumor Response (TTR)
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
Population: ITT. Number of participants analyzed = those who had a confirmed response on study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib + Gefitinib | Time to Tumor Response (TTR) | 16.0 weeks |
Secondary
Trough Plasma Concentrations (Ctrough) of Sunitinib
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | Trough Plasma Concentrations (Ctrough) of Sunitinib | Cycle 1, Day 1 (n=35) | 1.57 ng/mL | Standard Deviation 9.263 |
| Sunitinib + Gefitinib | Trough Plasma Concentrations (Ctrough) of Sunitinib | Cycle 1, Day 28 (n=33) | 33.16 ng/mL | Standard Deviation 13.915 |
| Sunitinib + Gefitinib | Trough Plasma Concentrations (Ctrough) of Sunitinib | Cycle 2, Day 1 (n=28) | 3.25 ng/mL | Standard Deviation 3.209 |
| Sunitinib + Gefitinib | Trough Plasma Concentrations (Ctrough) of Sunitinib | Cycle 2, Day 28 (n=27) | 35.50 ng/mL | Standard Deviation 11.957 |
| Sunitinib + Gefitinib | Trough Plasma Concentrations (Ctrough) of Sunitinib | Cycle 3, Day 1 (n=25) | 3.71 ng/mL | Standard Deviation 3.335 |
| Sunitinib + Gefitinib | Trough Plasma Concentrations (Ctrough) of Sunitinib | Cycle 3, Day 28 (n=24) | 35.97 ng/mL | Standard Deviation 12.462 |
Secondary
VEGF-C Concentration at Baseline
Concentration of VEGF-C at baseline.
Time frame: Baseline (Cycle 1, Day 1)
Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib + Gefitinib | VEGF-C Concentration at Baseline | 725.82 pg/mL | Standard Deviation 533.798 |
Secondary
VEGF-C Ratio to Baseline at Each Time Point
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | VEGF-C Ratio to Baseline at Each Time Point | Cycle 1, Day 28 (n=29) | 0.93 ratio | Standard Deviation 0.433 |
| Sunitinib + Gefitinib | VEGF-C Ratio to Baseline at Each Time Point | Cycle 2, Day 1 (n=26) | 0.86 ratio | Standard Deviation 0.315 |
| Sunitinib + Gefitinib | VEGF-C Ratio to Baseline at Each Time Point | Cycle 2, Day 28 (n=23) | 1.01 ratio | Standard Deviation 0.585 |
| Sunitinib + Gefitinib | VEGF-C Ratio to Baseline at Each Time Point | Cycle 3, Day 1 (n=22) | 1.09 ratio | Standard Deviation 0.573 |
| Sunitinib + Gefitinib | VEGF-C Ratio to Baseline at Each Time Point | Cycle 3, Day 28 (n=20) | 0.93 ratio | Standard Deviation 0.452 |
Secondary
VEGF Ratio to Baseline at Each Time Point
VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).
Time frame: Baseline to Cycle 3, Day 28 inclusive
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib + Gefitinib | VEGF Ratio to Baseline at Each Time Point | Cycle 1, Day 28 (n=29) | 2.29 ratio | Standard Deviation 1.269 |
| Sunitinib + Gefitinib | VEGF Ratio to Baseline at Each Time Point | Cycle 2, Day 1 (n=26) | 1.65 ratio | Standard Deviation 1.951 |
| Sunitinib + Gefitinib | VEGF Ratio to Baseline at Each Time Point | Cycle 2, Day 28 (n=23) | 2.65 ratio | Standard Deviation 1.956 |
| Sunitinib + Gefitinib | VEGF Ratio to Baseline at Each Time Point | Cycle 3, Day 1 (n=22) | 1.93 ratio | Standard Deviation 1.872 |
| Sunitinib + Gefitinib | VEGF Ratio to Baseline at Each Time Point | Cycle 3, Day 28 (n=20) | 2.26 ratio | Standard Deviation 1.195 |
Secondary
VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline
Concentration of VEGF at baseline.
Time frame: Baseline (Cycle 1, Day 1)
Population: ITT. Number of participants analyzed = number of subjects with soluble protein biomarkers at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib + Gefitinib | VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline | 63.79 pg/mL | Standard Deviation 43.437 |