OBJECTIVES:

Primary

• Compare the overall survival of patients with advanced renal cell carcinoma treated with interferon alfa-2b alone or interferon alfa-2b with bevacizumab.

Secondary

• Compare the time to disease progression and objective response rates in patients treated with these regimens.
• Determine the toxicity of interferon alfa-2b in combination with bevacizumab in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior nephrectomy (yes vs no) and number of risk factors for disease progression (0 vs 1-2 vs 3 or more). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive interferon alfa-2b subcutaneously (SC) three times a week.
• Arm II: Patients receive interferon alfa-2b as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then annually for up to 10 years after study entry.

PROJECTED ACCRUAL: A total of 700 patients (350 per treatment arm) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma (RCC)

  • Conventional clear cell carcinoma
  • Metastatic or unresectable disease

• The following characteristics and cellular types are excluded:

  • True papillary
  • Sarcomatoid features without a clear cell component
  • Chromophobe
  • Oncocytoma
  • Collecting duct tumor
  • Transitional cell carcinoma

• Measurable or nonmeasurable disease, including any of the following:

  • Unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., physical exam or chest x-ray) OR 10 mm by spiral CT scan or MRI

  • The following are considered nonmeasurable disease:

    • Small lesions
    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses that are not confirmed and followed by imaging techniques
    • Cystic lesions
    • Irradiated lesions, unless progression is documented after radiotherapy
• RCC paraffin tissue blocks or unstained slides must be available
• No evidence of prior or concurrent CNS metastases by MRI or CT scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No history of clinically significant bleeding

Hepatic

• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

• No proteinuria > 1+

  • Proteinuria ≥ 2+ allowed provided protein is < 2 g/24-hour urine collection

Cardiovascular

• No deep venous thrombosis within the past year
• No cerebrovascular accident within the past year
• No peripheral vascular disease with claudication on < 1 block
• No uncontrolled hypertension defined as blood pressure ≥160 mm Hg (systolic) and/or ≥ 90 mm Hg (diastolic) while on medication
• No New York Heart Association class II-IV congestive heart failure
• No angina pectoris requiring nitrate therapy
• No myocardial infarction within the past 6 months
• No other significant cardiovascular disease

Pulmonary

• No pulmonary embolus within the past year
• No ongoing hemoptysis

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study treatment
• No preexisting thyroid abnormality in which normal thyroid function cannot be maintained by medication
• No delayed wound healing, ulcers, or bone fractures
• No uncontrolled psychiatric disorder
• No other currently active* malignancy except nonmelanoma skin cancer NOTE: *Disease is not considered currently active if patient completed anticancer therapy and is considered to have < 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior systemic immunotherapy for RCC
• No prior thalidomide, anti-vascular endothelial growth factor (VEGF) therapy, VEGF receptor inhibitors, or antiangiogenic treatment of any kind
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• No prior systemic chemotherapy for RCC
• No concurrent chemotherapy

Endocrine therapy

• No concurrent systemic corticosteroid therapy except the following:

  • Topical and inhaled steroids
  • Replacement therapy for adrenal insufficiency
• No concurrent hormones except those administered for nondisease-related conditions (e.g., insulin for diabetes)

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• Prior palliative radiotherapy to metastatic lesions allowed provided at least 1 measurable or nonmeasurable lesion remains untreated
• No concurrent palliative radiotherapy

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• No other prior systemic investigational therapy for RCC
• No other prior adjuvant or neoadjuvant systemic therapy for RCC
• No concurrent full-dose oral or parenteral anticoagulation* NOTE: *Low-dose (1 mg) warfarin for maintenance of catheter patency and/or daily prophylactic aspirin is allowed