Vorinostat and Bevacizumab in Treating Patients With Unresectable or Metastatic Kidney Cancer

Inclusion Criteria

• •No known CNS metastasis
• •ECOG performance status 0-2
• •Life expectancy \> 6 months
• •LVEF ≥ 45%
• •Absolute neutrophil count ≥ 1,500/mm3
• •Platelet count ≥ 100,000/mm3
• •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• •AST/ALT ≤ 2.5 times ULN
• •Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• •PT/INR ≤ 1.5
• •Urine protein \< 1+ by urinalysis OR \< 1 g by 24-hour urine collection
• •Not pregnant
• •No nursing during and for 6 months after completion of study treatment
• •Negative pregnancy test
• •Fertile patients must use effective contraception for 2 weeks prior, during, and for 6 months after completion of study treatment
• •No other currently active malignancy defined as \> 30% risk of relapse upon completion of anticancer therapy, except nonmelanoma skin cancer
• •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA)
• •No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• •No evidence of bleeding diathesis or coagulopathy
• •No active bleeding or pathological conditions that carry high risk of bleeding (i.e., tumor involving major vessels or known varices)
• •No ongoing, active infection
• •No New York Heart Association class II-IV congestive heart failure
• •No angina pectoris requiring nitrate therapy
• •No cardiac arrhythmia
• •No myocardial infarction within the past 6 months
• •No history of cerebrovascular accident within the past 6 months
• •No uncontrolled hypertension (defined as systolic blood pressure (BP) \> 160 mm Hg and/or diastolic BP \> 90 mm Hg on medication)
• •No history of peripheral vascular disease
• •No psychiatric illness or social situation that would preclude study compliance
• •No other uncontrolled illness
• •No serious nonhealing wound, ulcer, or bone fracture
• •No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• •No significant traumatic injury in the past 28 days
• •At least 4 weeks since prior major surgery or open biopsy
• •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• •More than 4 weeks since prior radiotherapy
• •At least 2 weeks since prior tyrosine kinase inhibitor
• •Prior palliative radiotherapy to metastatic lesions allowed provided ≥ 1 measurable and/or evaluable lesion has not been irradiated
• •No more than 2 prior systemic treatments for metastatic disease, including immunotherapy, receptor tyrosine kinase inhibitor therapy, chemotherapy, or investigational therapy
• •No prior therapy with bevacizumab, vascular endothelial growth factor-trap, or histone deacetylase inhibitors, including valproic acid
• •No core biopsy within 1 week prior to day 1 of study treatment
• •No planned major surgery during study treatment
• •No concurrent combination antiretroviral therapy for HIV-positive patients
• •No other concurrent investigational agents
• •Concurrent stable-dose prophylactic anticoagulation (i.e., warfarin or low molecular weight heparin) allowed provided requirements for INR are met
• •Histologically confirmed renal cell carcinoma, clear cell component, unresectable or metastatic disease (patients with a primary tumor in place who are eligible for surgery are strongly encouraged to undergo a nephrectomy prior to study entry to increase potential survival)
• •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm with spiral CT scan
• •The following histologies are not allowed:
• •* Papillary, sarcomatoid carcinoma
• •* Chromophobe carcinoma
• •* Oncocytoma
• •* Collecting duct tumor
• •* Transitional cell carcinoma
• •WBC ≥ 3,000/mm\^3