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

SORCE: A Phase III Randomised Double-Blind Study Comparing Sorafenib With Placebo in Patients With Resected Primary Renal Cell Carcinoma at High or Intermediate Risk of Relapse

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. Giving sorafenib after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sorafenib is more effective than a placebo in treating kidney cancer.

PURPOSE: This randomized phase III trial is studying sorafenib to see how well it works compared with a placebo 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