CCI-779 and Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney Cancer

Inclusion Criteria:

Histologically confirmed metastatic or unresectable renal cell cancer

Must have a component of conventional clear cell histology

The following histologies are excluded:

True papillary
Sarcomatoid features without any clear cell component
Chromophobe
Oncocytoma
Collecting duct tumors
Transitional cell carcinoma
Measurable disease, defined as ≥ 1 lesion ≥ 2.0 cm in the longest diameter by conventional techniques OR ≥ 1.0 cm by spiral CT scan
Tumor tissue (from primary tumor or metastases) available AND patient is willing to donate blood for research studies (phase II only)
No CNS metastases by head CT scan or MRI
Performance status - ECOG 0-2
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9.0 g/dL
No evidence of bleeding diathesis or coagulopathy
No history of clinically significant bleeding or active bleeding
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
AST ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

PT/INR ≤ 1.5

Patients on full-dose warfarin or stable-dose low molecular weight heparin must have INR > 1.5 but ≤ 3
Creatinine ≤ 1.5 times ULN
Urine protein ≤ 1+ by dipstick or urinalysis
Urine protein < 1,000 mg on a 24-hour urine collection
No cerebrovascular accident within the past 6 months
No peripheral vascular disease with claudication on < 1 block
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 uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 160 mm Hg and/or diastolic BP ≥ 90 mm Hg despite medication
No cardiac arrhythmias
No other significant cardiovascular disease
No ongoing hemoptysis
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3-4 months after study participation
Fasting cholesterol ≤ 350 mg/dL
Triglycerides ≤ 1.5 times ULN (may achieve using lipid lowering agents)
No known hypersensitivity to recombinant human antibodies
No significant traumatic injury within the past 4 weeks
No serious or non-healing wound, ulcer, or bone fracture
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks
No pathological conditions that confer a high risk of bleeding (e.g., tumor involving major vessels or known varices)
No diabetes

No other currently active malignancy except nonmelanoma skin cancer

Patients are not considered to have a currently active malignancy if they have completed anticancer therapy AND are considered to be at < 30% risk of relapse
No other uncontrolled serious medical or psychiatric condition
At least 4 weeks since prior biologic response modifiers for metastatic disease
No prior bevacizumab or mTOR inhibitors
At least 4 weeks since prior chemotherapy for metastatic disease
Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1 measurable and/or evaluable lesion that has not been irradiated
At least 4 weeks since prior and no concurrent radiotherapy
Prior nephrectomy allowed
More than 4 weeks since prior major surgery or open biopsy
More than 1 week since prior core biopsy
No concurrent major surgery

At least 4 weeks (2 weeks for vascular endothelial growth factor [VEGF] receptor tyrosine kinase inhibitor [RTKI] therapy) since prior and no more than 2 therapies (phase II)

One of these therapies must have included a RTKI agent administered for a minimum of 4 weeks
Concurrent full-dose warfarin or low molecular weight heparin allowed provided dose is stable AND INR requirements are met
Concurrent zoledronate for bone metastases and/or hypercalcemia allowed provided therapy was initiated prior to study entry