SU011248 In The Treatment Of Patients With Bevacizumab (Avastin)-Refractory Metastatic Renal Cell Carcinoma

A Phase 2 Study Of SU011248 In The Treatment Of Patients With Bevacizumab-Refractory Metastatic Renal Cell Carcinoma

The purpose of this study is to test whether sunitinib (SU011248) has activity and is safe in patients with renal cell carcinoma (RCC) who have failed prior therapy with bevacizumab (Avastin) -based treatment.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Pfizer Investigational Site
    • Pasadena, California, United States, 91105
      • Pfizer Investigational Site
    • San Francisco, California, United States, 94115
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60637-1460
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Pfizer Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Pfizer Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5536
      • Pfizer Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • 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 proven renal cell carcinoma of clear cell histology with metastases
• Evidence of measurable disease
• Radiographic evidence of disease progression during or within 3 months of completion of bevacizumab-based treatment
• Prior radical or partial nephrectomy

Exclusion Criteria:

• Prior treatment with any other anti-angiogenic therapy other than bevacizumab
• Prior systemic treatment for RCC > 2 regimens
• History of or known brain metastases
• Serious acute or chronic illness or recent history of significant cardiac abnormality

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: 1	Drug: Sunitinib; 50 mg orally daily for 4 weeks followed by 2 weeks off treatment for approximately 1 year or until disease progression/unacceptable toxicity; after completion of 1 year, pts with clinical benefit can continue the study treatment in a separate continuation protocol; Other Names: SUTENT, SU011248,

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.	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Tumor Progression (TTP)	TTP was defined as the time from the date of first dose of study medication to the date of the first documentation of 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.	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Duration of Response (DR)	DR was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was only calculated for the subgroup of subjects with a confirmed objective response. DR was calculated as [the end date for DR minus first CR or PR that was subsequently confirmed +1]/7. Kaplan-Meier method was used.	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Overall Survival (OS)	OS was defined as the time from start of study treatment to date of death due to any cause. OS (in weeks) was calculated as [date of death minus first dose date +1]/7. For a subject not expiring, the OS time was censored on the last date of known contact that they were known to be alive. Subjects lacking data beyond the day of the first dose had their OS times censored at 1 day. Kaplan-Meier method was used.	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Progression Free Survival (PFS)	PFS was defined as the time from start of study medication to first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, 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.	4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Trough Plasma Concentrations (Cmin) of Sunitinib		Day 28 of Cycle 1 to Cycle 4
Trough Plasma Concentrations (Cmin) of SU012662		Day 28 of Cycle 1 to Cycle 4
Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662)		Day 28 of Cycle 1 to Cycle 4
Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A)	Plasma concentrations of VEGF-A that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.	Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)	Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.	Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)
Plasma Concentration of Placental Growth Factor (PlGF)	Plasma concentrations of PlGF that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.	Cycle 1 (Days 1, 14, and 28)
Plasma Concentration of VEGF-C	Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.	Cycle 1 (Days 1, 14, and 28)
Plasma Concentration of Soluble VEGF Receptor-2(sVEGFR-2)	Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were to have been analyzed by ELISA analysis; however, no data were collected.	1 year

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: August 9, 2004
• First Submitted That Met QC Criteria: August 10, 2004
• First Posted (Estimate): August 11, 2004

Study Record Updates

• Last Update Posted (Estimate): January 12, 2010
• Last Update Submitted That Met QC Criteria: January 6, 2010
• Last Verified: January 1, 2010

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
• Other Study ID Numbers: A6181039