Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer

NCT00324740 | Terminated Phase 1 Results DMC

• 4 other identifiers: NCI-2009-00095NCI-6896N01CM62204P30CA013330
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants With at Least One Dose Limiting Toxicity Associated With Vorinostat Concurrently Administered With Isotretinoin

  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

  Course 1, up to 28 days

• Maximum Tolerated Dose of Vorinostat in Combination With Isotretinoin

  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.

  Once 2 DLT events occur in patients, the preceding dose will be designated the maximum tolerated dose (MTD).

• Objective Response Rate

  The Response Evaluation Criteria in Solid Tumors (RECIST 1.0) was used and tumor responses were defined as complete response (CR), partial response (PR), stable disease (SD) or Progression

  Tumor measurements every 8 weeks until disease progression

Study Arms (1)

Treatment (vorinostat and isotretinoin)

EXPERIMENTAL

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

Interventions

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Treatment (vorinostat and isotretinoin)

isotretinoin DRUG

Given orally

Also known as: 13-CRA, Amnesteem, Cistane, Claravis, Sotret

Treatment (vorinostat and isotretinoin)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467-2490, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Vorinostat; Isotretinoin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Lisa Escobar-Peralta, Program Manager
• Organization: Montefiore Medical Center

lescobar@montefiore.org

718-379-6866

Study Officials

• David Nanus

  Montefiore Medical Center - Moses Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2006
• First Posted: May 11, 2006
• Study Start: March 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: May 1, 2014
• Last Updated: February 23, 2021
• Results First Posted: November 24, 2015

Record last verified: 2021-02

Locations

US (2)