Sorafenib in Treating Patients With Metastatic Kidney Cancer That Has Not Responded to Sunitinib or Bevacizumab

Study Overview
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Brief Summary
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RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with metastatic kidney cancer that has not responded to sunitinib or bevacizumab.

Detailed Description
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OBJECTIVES: Primary To determine the tumor burden reduction rate in patients with sunitinib malate- or bevacizumab-refractory, metastatic clear cell renal cell carcinoma treated with sorafenib tosylate. Secondary To determine the safety of sorafenib tosylate in these patients. To record the duration of tumor reduction, time to disease progression, and overall survival of patients treated with sorafenib tosylate. OUTLINE: Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma (RCC) Refractory to SU11248 or Bevacizumab Therapy

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: sorafenib tosylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma with a component of clear cell histology Metastatic disease Disease progression, as defined by RECIST criteria, after prior treatment with sunitinib malate or bevacizumab Patients must have received ≥ 1 course (4 weeks) of sunitinib malate or ≥ 2 doses of bevacizumab AND have RECIST-defined objective progression during or within 4 months after completing treatment with sunitinib malate or bevacizumab Measurable disease by RECIST criteria CNS metastases allowed provided patient has undergone prior surgery and/or radiotherapy AND has no evidence of further CNS disease progression by CT scan or MRI ≥ 2 weeks after treatment of CNS metastases PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% WBC ≥ 3,000/μL Absolute neutrophil count ≥ 1,500/μL Platelet count ≥ 75,000/μL Total bilirubin ≤ 1.5 times upper limit of normal (ULN) AST/ALT ≤ 2.5 times ULN Creatinine ≤ 2.0 times ULN Negative pregnancy test No significant cardiovascular disease, including any of the following: Congestive heart failure (New York Heart Association class III-IV heart disease) Active angina pectoris requiring nitrate therapy Uncontrolled dysrhythmias Cardiovascular event within the past 6 months (e.g., transient ischemic attack/cerebrovascular accident, myocardial infarction, or vascular surgery) PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 2 weeks since prior systemic therapy, radiotherapy, or major surgery and recovered No prior sorafenib tosylate No other concurrent investigational agents No other concurrent anticancer therapy No concurrent prophylactic growth factors

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib<br>Chemotherapy single agent systemic. Sorafenib given up to 600mg orally every 12 hours for up to 10 months (40 weeks). | Drug: sorafenib tosylate<br>* Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor targeting both tumor cells and the tumor vasculature. Patients with metastatic RCC meeting eligibility criteria will receive 400 mg BID of sorafenib in a single-arm phase II study. Treatment will be administered on an outpatient basis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Burden Reduction Rate (TBRR) | The primary endpoint of the study is defined as the percentage of patients who experience larger than or equal to 5% reduction in tumor burden as measured by RECIST-defined target lesions without progression of non-target lesions or the appearance of any new lesions, confirmed at least 4 weeks after first documentation. RECIST criteria will be used for the purpose of designating target lesions, calculating total tumor burden (the sum of the unidimensional measurement of target lesions) and defining disease progression.Additional RECIST-defined partial or complete responses will be recorded. | at 8 weeks (2cycles of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival measured in months and summarized using the Kaplan-Meier method. This will be calculated from the date of registration on-study to the dates of documented evidence of progression and death, respectively. | followed until progression or death for approximately 3 years | 
| Time to Progression | Time to objective progression will be measured from the start of treatment until the criteria for RECIST-defined progression are met, taking as reference the smallest measurements recorded since the treatment started, including baseline. Progression-free survival measured in months and summarized using the Kaplan-Meier method. | followed to progression for approximately 3 years | 
| Duration of Overall Response (Tumor Burden Reduction) | Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. | followed for overall response for approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clear cell renal cell carcinoma, recurrent renal cell cancer, stage IV renal cell cancer