A Randomized Phase III Trial Of Interferon Alfa-2B Or Interferon Alfa-2B Plus Bevacizumab In Patients With Advanced Renal Carcinoma

Inclusion Criteria

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