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

• Status: Completed
• Trial end date: 2013-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I/II trial is studying the side effects and best dose of vorinostat when given together with bevacizumab and to see how well they work in treating patients with unresectable or metastatic kidney cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving vorinostat together with bevacizumab may kill more tumor cells.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Bevacizumab; Immunoglobulins; Vorinostat

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