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