Sorafenib in Treating Patients at Risk of Relapse After Undergoing Surgery to Remove Kidney Cancer

OBJECTIVES:

• Compare disease-free survival of patients with resected primary renal cell carcinoma at high- or intermediate-risk of relapse treated with a placebo for 3 years vs a placebo for 2 years and sorafenib tosylate for 1 year vs sorafenib tosylate for 3 years.

OUTLINE: This is a randomized, placebo-controlled, double-blind, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive oral placebo twice daily for 3 years in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral sorafenib tosylate twice daily for 1 year and oral placebo twice daily for 2 years in the absence of disease progression or unacceptable toxicity.
• Arm III: Patients receive oral sorafenib tosylate twice daily for 3 years in the absence of disease progression or unacceptable toxicity.

Patients in arms I and II with progressive disease may cross over and receive treatment in arm III.

After completion of study treatment, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma (RCC)

• Clear cell or non-clear cell tumors allowed
• Intermediate- or high-risk disease (Leibovich score 3 to 11)
• Must have undergone surgery for RCC at least 4 weeks but no more than 3 months prior to study entry

• No evidence of residual macroscopic disease on post-operative CT scan after resection of RCC

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• WBC > 3,400/mm³
• Platelet count > 99,000/mm³
• Creatinine < 2.5 times upper limit of normal (ULN)
• Liver function tests < 1.5 times ULN
• Serum amylase < 1.5 times ULN
• PT/INR < 1.5 times ULN
• PTT < 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 9 months after completion of study treatment
• No cardiovascular conditions, including any of the following:

• Cardiac arrhythmias requiring anti-arrhythmic medication

• Beta-blockers and digoxin allowed
• Symptomatic coronary artery disease or ischemia
• Myocardial infarction within the past 6 months
• NYHA class II-IV congestive heart failure
• No active clinically serious bacterial or fungal infection
• No known history of HIV infection
• No chronic hepatitis B or C
• No other prior malignancy except carcinoma in situ of the cervix or adequately treated basal cell carcinoma
• No uncontrolled hypertension

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior treatment for RCC other than nephrectomy
• More than 30 days since prior and no other concurrent investigational therapy
• No concurrent medications that have adverse interactions with sorafenib tosylate including, but not limited to, any of the following:

• Rifampin
• Grapefruit juice
• Ritonavir
• Ketoconazole
• Itraconazole
• Hypericum perforatum (St John's wort)
• No concurrent bone marrow transplant or stem cell rescue
• No other concurrent drug that targets angiogenesis, especially VEGF or VEGF receptors (e.g., bevacizumab)
• No other concurrent drug that targets Ras-pathway or EGFR
• No other concurrent anticancer therapy (chemotherapy, immunotherapy, signal transduction inhibition, or hormonal therapy)
• Concurrent non-conventional therapies (e.g., herbs or acupuncture) and vitamin or mineral supplements allowed
• Concurrent bisphosphonates for prophylaxis of osteoporosis allowed