Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer
Recurrent Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Dose Limiting Toxicities Associated With Vorinostat Concurrently Administered With Isotretinoin [ Time Frame: Course 1, up to 28 days ] [ Designated as safety issue: Yes ]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
- Maximum Tolerated Dose of Vorinostat in Combination With Isotretinoin [ Time Frame: Once 2 DLT events occur in patients, the preceding dose will be designated the maximum tolerated dose (MTD). ] [ Designated as safety issue: Yes ]Hematologic: Any Grade 3/4 Thrombocytopenia and/or Grade 3/4 Neutropenia Non-Hematologic: Any >/= Grade3 non-hematologic toxicity considered by the investigator to be possibly related to study drug and/or any non-hematologic toxicity that results in a dose-delay of more than three weeks.
- Objective Response Rate [ Time Frame: Tumor measurements every 8 weeks until disease progression ] [ Designated as safety issue: No ]The phase II portion of the study ended early therefore the primary outcome of the objective response rate was not assessed.
|Study Start Date:||March 2006|
|Study Completion Date:||May 2014|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vorinostat and isotretinoin)
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.
Other Names:Drug: isotretinoin
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 II)
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 toxicity.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00324740
|United States, New York|
|Montefiore Medical Center - Moses Campus|
|Bronx, New York, United States, 10467-2490|
|Weill Medical College of Cornell University|
|New York, New York, United States, 10065|
|Principal Investigator:||David Nanus||Montefiore Medical Center - Moses Campus|