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