Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

This study has been terminated.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: May 10, 2006
Last updated: October 22, 2015
Last verified: June 2014
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.

Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Drug: vorinostat
Drug: isotretinoin
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.

Enrollment: 14
Study Start Date: March 2006
Study Completion Date: May 2014
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Drug: isotretinoin
Given orally
Other Names:
  • 13-CRA
  • Amnesteem
  • Cistane
  • Claravis
  • Sotret

Detailed Description:


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.


Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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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
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: David Nanus Montefiore Medical Center - Moses Campus
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00324740     History of Changes
Other Study ID Numbers: NCI-2009-00095, NCI-2009-00095, NCI-6896, N01CM62204, P30CA013330
Study First Received: May 10, 2006
Results First Received: July 20, 2015
Last Updated: October 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Diseases
Kidney Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2015