Phase I/II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With the VEGF Inhibitor Bevacizumab in Patients With Metastatic Renal Cell Carcinoma
I. Determine the safety and tolerability of vorinostat (SAHA) in combination with
bevacizumab in patients with unresectable or metastatic renal cell carcinoma. (Phase I) II.
Determine the recommended dosing in patients treated with this regimen. (Phase I) III.
Determine the proportion of patients who are progression-free at 6 months after receiving
this regimen. (Phase II) IV. Determine the clinical response rate in patients treated with
this regimen. (Phase II)
I. Determine the toxicity of this regimen in these patients. (Phase II) II. Determine time
to progression and duration of progression-free and overall survival in patients treated
with this regimen. (Phase II) III. Determine the pharmacodynamic effects in peripheral blood
mononuclear cells and tumors before and after treatment with this regimen in these patients.
(Phase II) IV. Determine the antiproliferative and apoptotic effects of this regimen in
these patients. (Phase II) V. Determine the antiangiogenic effects of this regimen in these
patients. (Phase II) VI. Determine the modulation of tumor metabolism and tumor blood flow
in patients treated with this regimen. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of vorinostat (SAHA) followed by a phase
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
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
After completion of study treatment, patients are followed at 4 weeks and then every 3
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
Johns Hopkins University
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|Peninsula Oncology and Hematology PA||Salisbury, Maryland 21801|