Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

NCT ID: NCT00324740

Last Updated: 2021-02-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2014-05-31

Brief Summary

This phase I/II trial is studying the side effects and best dose of isotretinoin when given together with vorinostat and to see how well they work in treating patients with advanced kidney cancer. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may cause kidney cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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.

Conditions

Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given orally

isotretinoin

Intervention Type: DRUG

Given orally

Interventions

vorinostat

Given orally

Intervention Type: DRUG

isotretinoin

Given orally

Intervention Type: DRUG

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; 13-CRA; Amnesteem; Cistane; Claravis; Sotret

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed renal cell carcinoma

• Advanced or metastatic disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or > 10 mm by spiral CT scan (phase II only)
• Failed ≥ 2 prior treatment regimens, including chemotherapy, immunotherapy (i.e., interleukin or interferon), biological agents (i.e., kinase inhibitors), or combinations thereof

• An overlap between classes of therapies given concurrently will be counted as 2 prior treatment regimens
• No known brain metastases
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 mg/dL
• AST and ALT < 2.5 times upper limit of normal
• Creatinine ≤ 2 mg/dL OR creatinine clearance > 50 mL/min
• Negative pregnancy test

Exclusion Criteria

• Not pregnant or nursing
• No history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA), isotretinoin, or other agents or components (e.g., parabens) used in this study
• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situation that would preclude study compliance
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy, including radiation, biologic, or chemotherapeutic agents, for renal cell carcinoma or other tumors
• No other concurrent investigational agents, valproic acid, or other retinoid

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Nanus

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center - Moses Campus

Locations

Weill Medical College of Cornell University

New York, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Countries

United States

Other Identifiers

NCI-2009-00095

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-6896

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62204

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA013330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00095

Identifier Type: -

Identifier Source: org_study_id