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

Carcinoma, Renal Cell Clinical Trial

Official title:

A Phase 1/2 Safety And Pharmacokinetic Study Of SU011248 In Combination With Gefitinib (Iressa) In Patients With Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00113529
• Other study ID #: A6181038
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 8, 2005
• Last updated: August 25, 2011
• Start date: October 2004
• Est. completion date: October 2008

Study information

• Verified date: August 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: October 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Gefitinib + Sunitinib
Until disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Ann Arbor	Michigan
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter	No
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.	From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter	No
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).	From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death due to cancer	No
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.	From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter	No
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.	From start of study treatment until death	No
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.	From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death	No
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.	From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year	No
Secondary	VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline	Concentration of VEGF at baseline.	Baseline (Cycle 1, Day 1)	No
Secondary	VEGF Ratio to Baseline at Each Time Point	VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).	Baseline to Cycle 3, Day 28 inclusive	No
Secondary	VEGF-C Concentration at Baseline	Concentration of VEGF-C at baseline.	Baseline (Cycle 1, Day 1)	No
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).	Baseline to Cycle 3, Day 28 inclusive	No
Secondary	Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline	Concentration of sVEGFR2 at baseline.	Baseline (Cycle 1, Day 1)	No
Secondary	sVEGFR2 Ratio to Baseline at Each Time Point	sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).	Baseline to Cycle 3, Day 28 inclusive	No
Secondary	Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline	Concentration of sVEGFR3 at baseline.	Baseline (Cycle 1, Day 1)	No
Secondary	sVEGFR3 Ratio to Baseline at Each Time Point	sVEGFR3 concentration at each time point divided by sVEGFR3 concentration at baseline (ratio to baseline).	Baseline to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	Yes
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
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).	Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive	No
Secondary	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)	No
Secondary	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)	No
Secondary	Ctrough of Gefitinib		prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28)	No

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