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

Study Overview
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Brief Summary
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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.

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

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Sunitinib<br>* 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<br>* Other names: SUTENT, SU011248,;|

What is the study measuring?
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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 |