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