A Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Combination With Isotretinoin (13-cis Retinoic Acid, 13-CRA) in the Treatment of Patients With Advanced Renal Cell Carcinoma
I. Determine the maximum tolerated dose and phase II dose of isotretinoin when given in
combination with vorinostat (SAHA) in patients with advanced renal cell carcinoma. (Phase I)
II. Define dose-limiting and other toxicities in patients treated with this regimen. (Phase
I) III. Determine the objective response rate of patients treated with this regimen. (Phase
I. Conduct a pharmacokinetic analysis of this regimen in these patients. (Phase I) II.
Conduct gene profiling analysis of pre-study, paraffin-embedded tissues from patients
treated with this regimen. (Phase I) III. Conduct correlative studies to identify the effect
of SAHA and isotretinoin on RAR-B, LRAT, and STAT1-3 expression. (Phase I)
OUTLINE: This is a multicenter, phase I, dose-escalation study of isotretinoin, followed by
a multicenter, phase II, prospective, non-randomized study.
Phase I: Patients receive oral vorinostat (SAHA) twice daily and oral isotretinoin twice
daily on days 3-5, 10-12, 17-19, and 24-26. Treatment repeats every 28 days in the absence
of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating
doses of isotretinoin until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 6 patients experience dose-limiting
Phase II: Patients receive SAHA as in phase I and isotretinoin as in phase I at the MTD
determined in phase I. Tissue and blood samples are obtained for biomarker/laboratory
studies in weeks 1 and 4.
Gene profile analysis is conducted on tumor tissue. After completion of study treatment,
patients are followed for 12 weeks.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting and other toxicities associated with vorinostat concurrently administered with isotretinoin
Defined as the occurrence of one or more of the following toxicities as graded by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Montefiore Medical Center
United States: Food and Drug Administration
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