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

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

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).

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Gefitinib + Sunitinib

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10021
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sunitinib + Gefitinib; Phase 1 - 37.5 mg Sunitinib 4/2 Schedule + 250 mg Gefitinib; 50 mg Sunitinib + 250 mg Gefitinib Phase 2 - 37.5 mg Sunitinib 4/2 Schedule + 250 mg Gefitinib	Drug: Gefitinib + Sunitinib; Until disease progression or unacceptable toxicity.; Other Names: Iressa, SU011248, SUTENT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
VEGF (Vascular Endothelial Growth Factor) Concentration at Baseline	Concentration of VEGF at baseline.	Baseline (Cycle 1, Day 1)
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
VEGF-C Concentration at Baseline	Concentration of VEGF-C at baseline.	Baseline (Cycle 1, Day 1)
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
Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline	Concentration of sVEGFR2 at baseline.	Baseline (Cycle 1, Day 1)
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
Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline	Concentration of sVEGFR3 at baseline.	Baseline (Cycle 1, Day 1)
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
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
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
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
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
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
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
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
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
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
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
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
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
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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Motzer RJ, Hudes GR, Ginsberg MS, Baum MS, Harmon CS, Kim ST, Chen I, Redman BG. Phase I/II trial of sunitinib plus gefitinib in patients with metastatic renal cell carcinoma. Am J Clin Oncol. 2010 Dec;33(6):614-8. doi: 10.1097/COC.0b013e3181c4454d.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: June 8, 2005
• First Submitted That Met QC Criteria: June 8, 2005
• First Posted (Estimate): June 9, 2005

Study Record Updates

• Last Update Posted (Estimate): August 29, 2011
• Last Update Submitted That Met QC Criteria: August 25, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Gefitinib
• Other Study ID Numbers: A6181038