This phase I/randomized phase II trial is studying the side effects and best dose of bevacizumab and to see how well it works when given together with or without MEDI-522 in treating patients with unresectable or metastatic kidney cancer. Monoclonal antibodies, such as bevacizumab and MEDI-522, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and MEDI-522 may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without MEDI-522 in treating kidney cancer.

PRIMARY OBJECTIVES:

I. To assess the appropriate dose of bevacizumab when administered with humanized monoclonal antibody MEDI-522 in patients with unresectable or metastatic renal cell carcinoma previously treated with sunitinib malate or sorafenib tosylate. (Phase I) II. To compare the progression-free survival of these patients treated with bevacizumab with versus without humanized monoclonal antibody MEDI-522. (Phase II) III. To evaluate the qualitative and quantitative toxicities of bevacizumab and humanized monoclonal antibody MEDI-522 in these patients. (Phase II) IV. To estimate overall survival and RECIST response rate (i.e., confirmed and unconfirmed, complete and partial responses) in both treatment arms. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of bevacizumab followed by a randomized phase II study.

PHASE I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and humanized monoclonal antibody MEDI-522 IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity until the recommended phase II dose (RPTD) of bevacizumab is determined.

PHASE II: Patients are stratified according to the number of prior treatment regimens for renal cell carcinoma (1 vs 2) and whether there is a clear cell component (yes vs no). Patients are randomized to 1 of 2 treatment arms:

ARM I: Patients receive bevacizumab (10 mg/kg) IV over 30-90 minutes on days 1 and 15.

ARM II: Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and humanized monoclonal antibody MEDI-522 (8 mg/kg) IV over 30 minutes on days 1, 8, 15, and 22.

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

After completion of study therapy, patients are followed periodically for up to 3 years.

Criteria:

• Histologically or cytologically confirmed renal cell carcinoma
• Metastatic or unresectable disease
• Must have received prior sunitinib malate or sorafenib tosylate for metastatic or unresectable disease
• Measurable disease
• No soft tissue disease that has been irradiated within the past 2 months
• More than 6 months since prior and no concurrent treated or untreated brain metastases
• Stable, treated brain metastases allowed provided they remained stable for more than 6 months
• Patients with clinical evidence of brain metastases must have a negative brain CT or MRI scan for metastatic disease
• Zubrod performance status 0-1
• Urine protein:creatinine ratio =< 0.5 OR urine protein < 1,000 mg by 24-hour collection
• Not be pregnant or nursing
• Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy
• No serious or non-healing wound, ulcer, or bone fracture
• No clinically relevant bleeding diathesis or coagulopathy
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No significant traumatic injury within the past 28 days
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No other prior malignancy, except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
• No New York Heart Association class II-IV congestive heart failure
• No unstable symptomatic arrhythmia requiring medication
• Chronic, controlled arrhythmias (e.g., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed
• None of the following cardiovascular conditions within the past 6 months: Arterial thrombosis, Unstable angina, Myocardial infarction, Cerebrovascular accident
• Must have controlled blood pressure, defined as systolic blood pressure (BP) =< 160 mm Hg and/or diastolic BP =< 90 mm Hg
• More than 7 days since prior core biopsy
• At least 14 days since completion of prior therapy and recovered
• At least 28 days since prior radiotherapy and recovered
• No prior radiotherapy to >= 25% of bone marrow
• No more than two prior systemic regimens for renal cell carcinoma (including adjuvant treatment)
• No prior bevacizumab or humanized monoclonal antibody MEDI-522
• No major surgical procedure or open biopsy within the past 28 days
• No concurrent need for a major surgical procedure
• Concurrent full-dose anticoagulation with warfarin allowed provided INR is between 2-3
• Concurrent low molecular weight heparin allowed
• No clinically significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)