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