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Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00324740
First received: May 10, 2006
Last updated: August 4, 2014
Last verified: June 2014

May 10, 2006
August 4, 2014
March 2006
February 2011   (final data collection date for primary outcome measure)
  • Dose limiting and other toxicities associated with vorinostat concurrently administered with isotretinoin [ Time Frame: Course 1 ] [ 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 isotretinoin and vorinostat administered in combination [ Time Frame: Course 1 ] [ Designated as safety issue: Yes ]
    Graded using the NCI CTCAE version 3.0.
  • Objective response rate of patients with advanced renal cell carcinoma treated with isotretinoin and vorinostat administered in combination [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Not Provided
Complete list of historical versions of study NCT00324740 on ClinicalTrials.gov Archive Site
Pharmacokinetics [ Time Frame: At weeks 1 and 5 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (enzyme inhibitor)
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.
Interventions:
  • Drug: vorinostat
  • Drug: isotretinoin
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
14
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
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception for 1 month before, during, and for 1 month after completion of study treatment
  • 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
  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
  • At least 4 weeks since prior radiotherapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • At least 6 weeks since prior chemoimmunotherapy
  • 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
Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00324740
NCI-2009-00095, NCI-2009-00095, NYWCCC-0511008257, CDR0000472916, NCI-6896, 0511008257, 6896, N01CM62204, P30CA013330
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
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