Vorinostat and Bevacizumab in Treating Patients With Unresectable or Metastatic Kidney Cancer
Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer
About this trial
This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma
Eligibility Criteria
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
Sites / Locations
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Peninsula Oncology and Hematology PA
- University of Wisconsin Hospital and Clinics
Arms of the Study
Arm 1
Experimental
Arm I
Phase I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I.