Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00589472

Purpose

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin, and leuprolide, may lessen the amount of androgens made by the body. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving androgen deprivation therapy and vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving androgen deprivation therapy together with vorinostat followed by radical prostatectomy works in treating patients with localized prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Drug: bicalutamide Drug: goserelin Drug: leuprolide acetate Drug: vorinostat Genetic: gene expression analysis Genetic: microarray analysis Genetic: reverse transcriptase-polymerase chain reaction Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery	Phase II

MedlinePlus related topics: Cancer Prostate Cancer Surgery

Drug Information available for: Leuprolide Goserelin Leuprolide acetate Bicalutamide Suberoylanilide hydroxamic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Neoadjuvant Androgen Depletion in Combination With Vorinostat Followed by Radical Prostatectomy for Localized Prostate Cancer: Total Androgen-Receptor Gene Expression Targeted Therapy (TARGET)

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

Primary Outcome Measures:

Pathologic complete response at the time of surgery [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pre- and post-treatment levels of PSA, testosterone, DHT, DHEA, and DHEA-S in blood and radical prostatectomy specimens [ Designated as safety issue: No ]
Pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate tissue [ Designated as safety issue: No ]
Gene and protein expression analysis including AR target genes, PSA and TMPRSS2 (transmembrane protease, serine 2), in pre-treatment biopsy and post-treatment radical prostatectomy specimens [ Designated as safety issue: No ]
Exploratory gene microarray analysis [ Designated as safety issue: No ]
Safety and tolerability of androgen depletion therapy in combination with vorinostat (SAHA) as assessed by physical examinations, adverse events, and laboratory assessments [ Designated as safety issue: Yes ]

Estimated Enrollment:	38
Study Start Date:	November 2007
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the rate of pathologic complete response in patients with localized prostate cancer treated with androgen depletion therapy (ADT) and vorinostat (SAHA) before radical prostatectomy.

Secondary

Determine and evaluate pre- and post-treatment levels of PSA, testosterone, DHT, DHEA, and DHEA-S in blood.
Determine and evaluate pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate tissue.
Determine and evaluate gene and protein expression analysis including AR target genes, PSA and TMPRSS2 (transmembrane protease, serine 2), in pre-treatment biopsy and post-treatment radical prostatectomy specimens.
Perform exploratory gene microarray analysis.
Determine and evaluate the safety and tolerability of ADT in combination with vorinostat as assessed by physical examinations, adverse events, and laboratory assessments.

OUTLINE: This is a multicenter study.

Patients receive oral bicalutamide once daily for 1 month and leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) once a month until surgery. Patients also receive oral vorinostat (SAHA) once daily beginning on the first day of androgen depletion therapy and continuing for up to 8 weeks or until the day of surgery. Patients then undergo an open or laparoscopic radical prostatectomy. Patients with positive surgical margins undergo immediate adjuvant external beam radiotherapy to the prostatic fossa, based on the judgment of the treating physician.

Patients undergo tissue sample collection at baseline and during surgery for laboratory correlative studies. Biomarker expression analysis is performed on the samples by quantitative real time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) for HDAC-regulated target genes, AR and AR-regulated genes, PSA and TMPRSS2. If adequate material is available, fresh frozen tissue is analyzed by microarray analysis for predictors of response and resistance to therapy. Hormonal levels are also measured in these tissue samples. Patients also undergo blood sample collection periodically to measure hormone and PSA levels.

After completion of study therapy, patients are followed every 3 months for up to 1 year.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the prostate
- At least 3 biopsy cores positive for cancer, of which at least 1 core demonstrates > 30% involvement with tumor
Confirmation of localized disease by MRI with endorectal probe, if available
Serum PSA < 100 ng/mL
Candidate for radical prostatectomy
No evidence of small cell, transitional cell, or neuroendocrine pathologic features
No evidence of distant disease on CT scan or MRI of the abdomen and pelvis and on radionuclide bone scan (with plain film or MRI confirmation as clinically indicated)

PATIENT CHARACTERISTICS:

Karnofsky performance status 80-100%
WBC > 3,000/µL
Platelet count > 150,000/µL
Creatinine < 2 mg/dL
Bilirubin < 1.5 times upper limit of normal (ULN)
AST/ALT < 2 times ULN
Adequate cardiac function (evidence of cardiac disease should be evaluated to determine appropriateness of patient as a surgical candidate)
- May have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, if otherwise deemed to be suitable for radical prostatectomy
Must use adequate contraceptive methods during and for at least 3 months after completion of study therapy
No history of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat (SAHA)
No concurrent uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
No psychiatric illness/social situation that would compromise compliance with study requirements
No currently active secondary malignancy (as determined by the treating physician) other than nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

No prior hormonal therapy (e.g., 5-alpha-reductase inhibitors, gonadotropin hormone releasing analogs, steroids, megestrol acetate, or nonstudy-related antiandrogens) with the intent to treat the malignancy
No prior chemotherapy or herbal medications administered with the intent to treat the malignancy
At least 2 weeks since prior valproic acid
No concurrent valproic acid to treat prostate cancer
No other concurrent antineoplastic therapy
Concurrent systemic anticoagulation allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589472

Locations

United States, California
Jonsson Comprehensive Cancer Center at UCLA	Recruiting
Los Angeles, California, United States, 90095-1781
Contact: Clinical Trials Office - Jonsson Comprehensive Cancer Center a 888-798-0719
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Susan Slovin, MD, PhD 646-422-4470
United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Peter Nelson, MD 206-667-3377
Canada, British Columbia
Prostate Centre at Vancouver General Hospital	Recruiting
Vancouver, British Columbia, Canada, V5Z 355
Contact: Martin E. Gleave, MD 604-875-5003

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Susan Slovin, MD, PhD	Memorial Sloan-Kettering Cancer Center
Investigator:	Howard I. Scher, MD	Memorial Sloan-Kettering Cancer Center

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:	Memorial Sloan-Kettering Cancer Center ( David Paul Kelsen )
Study ID Numbers:	CDR0000579559, MSKCC-06160, MSKCC IRB 06-160
Study First Received:	December 20, 2007
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00589472 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
adenocarcinoma of the prostate

Study placed in the following topic categories:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Genital Neoplasms, Male
Prostatic Diseases
Hormone Antagonists
Vorinostat
Goserelin
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Genital Diseases, Male
Hormones

Androgen Antagonists
Analgesics, Non-Narcotic
Leuprolide
Bicalutamide
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Adenocarcinoma
Prostatic Neoplasms
Androgens

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Prostatic Diseases
Genital Neoplasms, Male
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Reproductive Control Agents
Hormones
Neoplasms by Site
Sensory System Agents
Leuprolide

Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Antineoplastic Agents, Hormonal
Vorinostat
Enzyme Inhibitors
Genital Diseases, Male
Protective Agents
Pharmacologic Actions
Neoplasms
Androgen Antagonists
Analgesics, Non-Narcotic
Fertility Agents, Female
Fertility Agents
Bicalutamide

ClinicalTrials.gov processed this record on May 07, 2009