RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Interferon alfa may interfere with the growth of tumor cells and slow the growth of kidney cancer. Sorafenib may help interferon alfa work better by making tumor cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving sorafenib with interferon alfa works in treating patients with metastatic or unresectable kidney cancer.

OBJECTIVES:

Primary

• Determine the response (confirmed complete and partial response) in patients with metastatic or unresectable renal cell cancer treated with sorafenib and interferon alfa.

Secondary

• Determine the probability of treatment failure at 6 months in patients treated with this regimen.
• Determine the median overall survival of patients treated with this regimen.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Correlate, preliminarily, tumor response with measures of increased signaling through the Ras-Raf pathway (p-MAPK, p-JNK, p-p38, and p-AKT) and von Hippel-Lindau gene status in patients treated with this regimen.
• Correlate changes in levels of interleukin-6 and tumor markers of hypoxia, including PAI-1, VEGF, and osteopontin, with clinical outcomes in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28 and interferon alfa subcutaneously on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 8-9 months.

• Biological: recombinant interferon alfa
• Drug: sorafenib tosylate

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell cancer (RCC)

  • Metastatic (M1) or unresectable (M0) disease

  • Must have a component of clear cell RCC

    • Patients with any of the following are not eligible:

      • True papillary RCC
      • Sarcomatoid features without any clear cell component
      • Chromophobe
      • Oncocytoma
      • Collecting duct tumors
      • Transitional cell carcinoma

• Measurable disease

  • Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease

• No prior or current brain metastases

  • Patients with clinical suspicion of brain metastases must have a negative brain CT scan or MRI AND have no new symptoms of brain metastases since radiographic evaluation

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin normal
• SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)

Renal

• Creatinine normal (≤ 2 times ULN for patients who have undergone prior nephrectomy) OR
• Creatinine clearance ≥ 60 mL/min

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Able to swallow oral medication intact
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer that is in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior interferon, interleukin-2, or other biologic response modifiers for RCC
• No prior antiangiogenic therapy for RCC

Chemotherapy

• No prior chemotherapy for RCC

Endocrine therapy

• No prior hormonal therapy for RCC
• Prior thyroid medications allowed

• No concurrent systemic corticosteroid therapy

  • Concurrent topical and/or inhaled steroids allowed

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to ≥ 25% of bone marrow

Surgery

• At least 4 weeks since prior surgery and recovered
• Prior resection of the primary tumor in patients with metastatic disease allowed

Other

• No prior experimental systemic therapy for RCC
• No other prior systemic therapy for RCC

• No concurrent inhibitors of CYP3A4 enzyme, including any of the following:

  • Ketoconazole
  • Itraconazole
  • Ritonavir
  • Grapefruit juice
  • Cyclosporine
  • Carbamazepine
  • Phenytoin
  • Phenobarbital