Vorinostat and Isotretinoin in Treating Patients With Advanced Kidney Cancer - Full Text View

Sponsor:	Weill Medical College of Cornell University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00324740

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Kidney Cancer	Drug: isotretinoin Drug: vorinostat Genetic: gene expression analysis Genetic: microarray analysis Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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:

MedlinePlus related topics: Cancer Kidney Cancer

Drug Information available for: Suberoylanilide hydroxamic acid Isotretinoin

U.S. FDA Resources

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

Primary Outcome Measures:

Dose-limiting toxicities [ Designated as safety issue: Yes ]
Maximum tolerated dose [ Designated as safety issue: Yes ]
Objective response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	March 2006
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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)
Define dose-limiting and other toxicities in patients treated with this regimen. (Phase I)
Determine the objective response rate of patients treated with this regimen. (Phase II)

Secondary

Conduct a pharmacokinetic analysis of this regimen in these patients. (Phase I)
Conduct gene profiling analysis of pre-study, paraffin-embedded tissues from patients treated with this regimen. (Phase I)
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.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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 componenets (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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324740

Locations

United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine	Recruiting
Bronx, New York, United States, 10461
Contact: Clinical Trials Office - Albert Einstein Cancer Center at Albe 718-904-2730 aecc@aecom.yu.edu
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Clinical Trials Office - Herbert Irving Comprehensive Cancer C 212-305-8615
Mount Sinai Medical Center	Recruiting
New York, New York, United States, 10029
Contact: Max W. Sung, MD 212-241-7902 max.sung@mssm.edu
New York Weill Cornell Cancer Center at Cornell University	Recruiting
New York, New York, United States, 10021
Contact: Clinical Trials Office - New York Weill Cornell Cancer Center 212-746-1848
NYU Cancer Institute at New York University Medical Center	Recruiting
New York, New York, United States, 10016
Contact: Anna C. Ferrari, MD 212-731-5389 anna.ferrari@nyumc.org

Sponsors and Collaborators

Weill Medical College of Cornell University

National Cancer Institute (NCI)

Investigators

Study Chair:

David M. Nanus, MD

Weill Medical College of Cornell University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Albert Einstein Cancer Center at Albert Einstein College of Medicine ( Joseph A. Sparano )
Study ID Numbers:	CDR0000472916, NYWCCC-0511008257, NCI-6896
Study First Received:	May 10, 2006
Last Updated:	June 9, 2009
ClinicalTrials.gov Identifier:	NCT00324740 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent renal cell cancer
stage III renal cell cancer
stage IV renal cell cancer

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Urogenital Neoplasms
Urologic Neoplasms
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Sensory System Agents
Therapeutic Uses
Isotretinoin
Anti-Inflammatory Agents, Non-Steroidal
Kidney Diseases

Analgesics
Dermatologic Agents
Neoplasms by Histologic Type
Vorinostat
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Analgesics, Non-Narcotic
Carcinoma, Renal Cell
Peripheral Nervous System Agents
Adenocarcinoma
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010