Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer

Inclusion Criteria:

Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion
Patients will be required to have measurable metastatic disease that is not curable by standard radiation therapy or surgery; all sites must be assessed within 4 weeks prior to study entry

Previous nephrectomy is required with the following exceptions:

Primary tumor =< 5 cm, or
Extensive liver (> 30% of liver parenchymal) or multiple (> 5) bone metastases, making nephrectomy a clinically questionable procedure
Unresectable primary tumor due to invasion into adjacent organs or encasing the aorta or vena cava
No prior cytotoxic chemotherapy; a maximum of one prior regimen of either vaccine or cytokine-based immunotherapy disease is permitted
No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap; no prior therapy with bevacizumab, mammalian target of rapamycin (mTOR) inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed; thalidomide or interferon alpha (IFNalpha) are allowed either for adjuvant therapy or stage IV disease
No immunotherapy within 4 weeks of randomization; toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment
Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization
No history or clinical evidence of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of greater than 12 weeks
Hemoglobin (Hgb) >= 9.0 g/dL (transfusions allowed prior to enrollment)
White blood count (WBC) >= 3,000/mm^3
Absolute granulocyte count (AGC) >= 1,200/mm^3
Platelet count >= 100,000/mm^3
Serum creatinine =< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 55 ml/min
Total bilirubin =< 1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (or =< 5.0 x ULN in the presence of liver metastases)
International normalized ratio (INR) =< 1.5
Activated partial thromboplastin time (aPTT) within normal limits
Fasting cholesterol < 350 mg/dL (9.0 mmol/L)
Fasting triglycerides < 400 mg/dL (4.56 mmol/L)
Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for >= 5 years prior to the time of randomization
No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab
No history of bleeding diathesis or coagulopathy
Any condition that impairs patient's ability to swallow pills will make patient ineligible
No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization
No anticipated need for major surgery during the course of the study
No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be =< 1.5)

No clinically significant cardiovascular disease, defined as one of the following:

Patients with uncontrolled hypertension (blood pressure > 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =< 150/100 mm/Hg on stable antihypertensive regimen are eligible
Myocardial infarction or unstable angina < 24 weeks prior to registration
New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
Grade II or greater peripheral vascular disease
No serious, non-healing wound, ulcer, or bone fracture

No significant proteinuria at baseline; urine protein must be screened within 2 weeks prior to randomization by urine analysis for urine protein creatinine (UPC) ratio; if UPC ratio is > 0.5, 24-hour urine protein is to be obtained and the level must be < 1000 mg for patient enrollment

NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 or psychiatric illness/social situations that would limit compliance with study requirements

Patients currently taking any of the following cytochrome P450 enzyme-inducing drugs are ineligible:

Phenytoin
Carbamazepine
Phenobarbital
Rifampin
Pregnant and breastfeeding women are excluded from the study; breastfeeding should be discontinued while receiving therapy; patients must have pregnancy test within 7 days prior to patient randomization if woman is of child-bearing capacity
Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study