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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00113529
First received: June 8, 2005
Last updated: August 25, 2011
Last verified: August 2011
  Purpose

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).


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: Gefitinib + Sunitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Safety And Pharmacokinetic Study Of SU011248 In Combination With Gefitinib (Iressa) In Patients With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Time to Tumor Response (TTR) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DR) [ 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter ] [ Designated as safety issue: No ]
    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) [ Time Frame: From start of study treatment until death ] [ Designated as safety issue: No ]
    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) [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter or death ] [ Designated as safety issue: No ]
    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 [ Time Frame: From start of treatment until Day 28 of Cycles 1 to 4, Day 28 of even cycles thereafter up until 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
    Concentration of VEGF at baseline.

  • VEGF Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    VEGF concentration at each time point divided by VEGF concentration at baseline (ratio to baseline).

  • VEGF-C Concentration at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
    Concentration of VEGF-C at baseline.

  • VEGF-C Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
    Concentration of sVEGFR2 at baseline.

  • sVEGFR2 Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    sVEGFR2 concentration at each time point divided by sVEGFR2 concentration at baseline (ratio to baseline).

  • Soluble VEGF Receptor 3 (sVEGFR3) Concentration at Baseline [ Time Frame: Baseline (Cycle 1, Day 1) ] [ Designated as safety issue: No ]
    Concentration of sVEGFR3 at baseline.

  • sVEGFR3 Ratio to Baseline at Each Time Point [ Time Frame: Baseline to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in VEGFC by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in VEGFR2 by Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] Versus PD) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Cycle 1, Day 1) to Cycle 3, Day 28 inclusive ] [ Designated as safety issue: No ]
    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 [ Time Frame: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • Ctrough of Gefitinib [ Time Frame: prior to dosing on Cycle 1 (Days 1, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28) ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: October 2004
Study Completion Date: October 2008
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Iressa, SU011248, SUTENT

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113529

Locations
United States, Michigan
Pfizer Investigational Site
Ann Arbor, Michigan, United States, 48109
United States, New York
Pfizer Investigational Site
New York, New York, United States, 10021
United States, Pennsylvania
Pfizer Investigational Site
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00113529     History of Changes
Other Study ID Numbers: A6181038
Study First Received: June 8, 2005
Results First Received: March 1, 2010
Last Updated: August 25, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Gefitinib
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014