Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00324740
Recruitment Status : Terminated
First Posted : May 11, 2006
Results First Posted : November 24, 2015
Last Update Posted : November 24, 2015
Information provided by (Responsible Party):
National Cancer Institute (NCI)

May 10, 2006
May 11, 2006
July 20, 2015
November 24, 2015
November 24, 2015
March 2006
February 2011   (Final data collection date for primary outcome measure)
  • Dose Limiting Toxicities Associated With Vorinostat Concurrently Administered With Isotretinoin [ Time Frame: Course 1, up to 28 days ]
    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). ]
    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 ]
    The phase II portion of the study ended early therefore the primary outcome of the objective response rate was not assessed.
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Complete list of historical versions of study NCT00324740 on Archive Site
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Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer
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
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.


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.

Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Recurrent Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • 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
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
  • Drug: isotretinoin
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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May 2014
February 2011   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
21 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
NCI-2009-00095 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-6896 ( Other Identifier: NCI/CTEP )
N01CM62204 ( U.S. NIH Grant/Contract )
P30CA013330 ( U.S. NIH Grant/Contract )
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National Cancer Institute (NCI)
National Cancer Institute (NCI)
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Principal Investigator: David Nanus Montefiore Medical Center - Moses Campus
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP