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

Pfizer1 site in 1 country42 target enrollmentOctober 2004

ConditionsCarcinoma, Renal Cell

InterventionsGefitinib + Sunitinib

DrugsGefitinib + Sunitinib

Overview

Phase: Phase 1
Intervention: Gefitinib + Sunitinib
Conditions: Carcinoma, Renal Cell
Sponsor: Pfizer
Enrollment: 42
Locations: 1
Primary Endpoint: Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
Status: Completed
Last Updated: 14 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

October 2004

End Date

October 2008

Last Updated

14 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

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

Intervention: Gefitinib + Sunitinib

Outcomes

Primary Outcomes

Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)

Time Frame: 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 Outcomes

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))
Time to Tumor Response (TTR)(From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter)
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)
Time to Tumor Progression (TTP)(From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter)
Overall Survival (OS)(From start of study treatment until death)
Progression-Free Survival (PFS)(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(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(Baseline (Cycle 1, Day 1))
VEGF Ratio to Baseline at Each Time Point(Baseline to Cycle 3, Day 28 inclusive)
VEGF-C Concentration at Baseline(Baseline (Cycle 1, Day 1))
VEGF-C Ratio to Baseline at Each Time Point(Baseline to Cycle 3, Day 28 inclusive)
Soluble VEGF Receptor 2 (sVEGFR2) Concentration at Baseline(Baseline (Cycle 1, Day 1))
sVEGFR2 Ratio to Baseline at Each Time Point(Baseline to Cycle 3, Day 28 inclusive)
Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline(Baseline (Cycle 1, Day 1))
sVEGFR3 Ratio to Baseline at Each Time Point(Baseline to Cycle 3, Day 28 inclusive)
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 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 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 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 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 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 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 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 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 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 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 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 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)
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))