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Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer

Intervention: vorinostat (Drug); isotretinoin (Drug); pharmacological study (Other); laboratory biomarker analysis (Other)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
David Nanus, Principal Investigator, Affiliation: Montefiore Medical Center - Moses Campus


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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Dose limiting and other toxicities associated with vorinostat concurrently administered with isotretinoin

Maximum tolerated dose of isotretinoin and vorinostat administered in combination

Objective response rate of patients with advanced renal cell carcinoma treated with isotretinoin and vorinostat administered in combination

Secondary outcome: Pharmacokinetics

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.


Minimum age: 21 Years. Maximum age: N/A. Gender(s): Both.


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


- 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

Locations and Contacts

Montefiore Medical Center - Moses Campus, Bronx, New York 10467-2490, United States

Weill Medical College of Cornell University, New York, New York 10065, United States

Additional Information

Starting date: March 2006
Last updated: August 4, 2014

Page last updated: August 23, 2015

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