Bevacizumab and Interleukin-2 in Treating Patients With Metastatic Kidney Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed renal cell cancer

  • Metastatic disease
  • More than 75% clear cell histology
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No prior refractory disease, defined as clinical or radiologic progression, during or within 3 months after completion of prior interleukin-2 (IL-2)

• Nominally "good" or "intermediate" risk disease, meeting ≥ 4 out of 5 of the following criteria:

  • Hemoglobin > 10 g/dL (except for patients with hereditary hemoglobinopathy)
  • ECOG performance status 0-1 (required)

  • Calcium normal (corrected)

    • Patients with hypercalcemia due to malignancy allowed provided it has been controlled for > 1 month
  • Primary tumor treated or resected by complete nephrectomy, partial nephrectomy, radiofrequency ablation, or other local ablation
  • Lactic dehydrogenase < 1.5 times upper limit of normal (ULN)
• No history of or current brain or CNS metastasis by CT scan or MRI within the past 30 days
• Performance status - ECOG 0-1
• More than 4 months
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 75,000/mm^3
• No history of bleeding diathesis
• PTT < 1.5 times ULN
• INR < 1.5
• Bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN
• No chronic hepatitis B or C
• Creatinine ≤ 2.0 mg/dL
• No proteinuria* by dipstick urinalysis
• Urine protein ≤ 1,000 mg by 24-hour urine collection
• No symptomatic congestive heart failure
• No uncontrolled hypertension, defined as systolic blood pressure (BP) > 160 mm Hg and diastolic BP > 90 mm Hg
• No cardiac arrhythmia
• No peripheral vascular disease ≥ grade 2
• No clinically significant peripheral artery disease

• None of the following arterial thromboembolic events within the past 6 months:

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina pectoris
  • Myocardial infarction
• Not pregnant
• No nursing during and for 3 months after completion of study treatment
• Negative pregnancy test
• Fertile patients must use effective contraception before, during, and for 3 months after completion of study treatment
• No active infection requiring parenteral antibiotics
• No known HIV positivity
• No history of allergic reaction to antibody drugs or IL-2
• No psychiatric illness or social situation that would preclude study compliance
• No non-healing wound or fracture
• No insulin-dependent diabetes
• No other uncontrolled illness
• No other malignancy requiring active treatment within the past 2 years except nonmelanoma skin cancer
• No prior bevacizumab
• At least 6 months since prior immunotherapy containing IL-2
• At least 2 months since prior investigational antibodies
• More than 4 weeks since prior conventional cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent corticosteroids except replacement corticosteroids for adrenal insufficiency OR inhaled steroids for chronic obstructive pulmonary disease, asthma, or allergic rhinitis
• More than 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to the only site of measurable disease unless there has been subsequent disease progression
• More than 4 weeks since prior major surgery
• At least 24 hours since prior minor surgical procedure, placement of vascular access device, or fine needle aspiration
• At least 30 days since prior and no other concurrent investigational agents

• More than 10 days since prior anticoagulants

  • Low-dose anticoagulants for maintenance of vascular access device patency allowed
• No concurrent therapeutic warfarin, including warfarin for treatment of deep vein thrombosis or pulmonary embolism
• No other concurrent anticancer therapy