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

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-11-30

Study Completion Date

2010-06-30

Brief Summary

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This phase II trial studies how well androgen deprivation therapy and vorinostat followed by radical prostatectomy works in treating patients with prostate cancer that has not spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, goserelin acetate, and leuprolide acetate, 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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the rate of pathologic complete response in patients with localized prostate cancer treated with androgen depletion therapy (ADT) and oral vorinostat administered for a minimum of 6 weeks and maximum of 8 weeks before radical prostatectomy.

SECONDARY OBJECTIVES:

I. To determine and evaluate pre- and post-treatment levels of prostate-specific antigen (PSA), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-dulfate (DHEA-S) in blood.

II. To determine and evaluate pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate.

III. To determine and evaluate gene and protein expression analysis including androgen receptor (AR) target genes, PSA and TMPRSS2 (transmembrane protease, serine 2), in pre-treatment biopsy and post-treatment radical prostatectomy.

IV. To determine and evaluate exploratory gene microarray analysis. V. To determine and evaluate the safety and tolerability of ADT in combination with vorinostat (SAHA) as assessed by physical examinations, adverse events, and laboratory assessments.

OUTLINE:

Patients receive bicalutamide orally (PO) once daily (QD) for 1 month and leuprolide acetate intramuscularly (IM) or goserelin acetate subcutaneously (SC) once a month until surgery. Patients also receive vorinostat PO QD 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.

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

Conditions

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Prostate Adenocarcinoma Stage I Prostate Cancer Stage IIA Prostate Cancer Stage IIB Prostate Cancer Stage III Prostate Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (Antihormone therapy and enzyme inhibitor therapy)

Patients receive bicalutamide PO QD for 1 month and leuprolide acetate IM or goserelin acetate SC once a month until surgery. Patients also receive vorinostat PO QD 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.

Group Type EXPERIMENTAL

Bicalutamide

Intervention Type DRUG

Given PO

Goserelin Acetate

Intervention Type DRUG

Given SC

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Leuprolide Acetate

Intervention Type DRUG

Given IM

Therapeutic Conventional Surgery

Intervention Type PROCEDURE

Undergo radical prostatectomy

Vorinostat

Intervention Type DRUG

Given PO

Interventions

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Bicalutamide

Given PO

Intervention Type DRUG

Goserelin Acetate

Given SC

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Leuprolide Acetate

Given IM

Intervention Type DRUG

Therapeutic Conventional Surgery

Undergo radical prostatectomy

Intervention Type PROCEDURE

Vorinostat

Given PO

Intervention Type DRUG

Other Intervention Names

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Casodex Cosudex ICI 176,334 ICI 176334 ZDX Zoladex A-43818 Abbott 43818 Abbott-43818 Carcinil Depo-Eligard Eligard Enanton Enantone Enantone-Gyn Ginecrin LEUP Leuplin Leuprorelin Acetate Lucrin Lucrin Depot Lupron Lupron Depot Lupron Depot-3 Month Lupron Depot-4 Month Lupron Depot-Ped Procren Procrin Prostap TAP-144 Trenantone Uno-Enantone Viadur L-001079038 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

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Inclusion Criteria

* Histologic documentation of prostatic adenocarcinoma in 3 or more biopsy cores, of which at least 1 core demonstrates \> 30% involvement with tumor; confirmation of localized disease by magnetic resonance imaging (MRI) with endorectal probe if available
* No evidence of distant disease on a:

* Computed tomography (CT) or MRI of the abdomen and pelvis
* Radionuclide bone scan (with plain film or MRI confirmation as clinically indicated)
* Appropriate candidate for radical prostatectomy

* Adequate cardiac function (evidence of cardiac disease should be evaluated to determine appropriateness of patient as a surgical candidate)
* Candidates may have a history of deep vein thrombosis, pulmonary embolism, and/or cerebrovascular accident, or require concomitant systemic anticoagulation, if otherwise deemed to be suitable for radical prostatectomy
* White blood cell (WBC) \> 3000/uL
* Platelets \> 150,000/uL
* Creatinine \< 2 mg/dL
* Serum PSA \< 100 ng/mL
* Bilirubin \< 1.5 X ULN (institutional upper limits of normal)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2 X ULN
* Karnofsky performance status \> 70%
* Willingness to undergo pretreatment transrectal ultrasound-guided prostate needle biopsy (optional)
* Willingness to use adequate contraceptive methods during study therapy and for at least 3 months after completion of therapy
* Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

* Evidence of small-cell, transitional-cell, or neuroendocrine pathologic features
* Prior hormonal therapy with (e.g. 5-alpha-reductase inhibitors, gonadotropin hormone releasing analogs, steroids, megestrol acetate, or nonstudy-related antiandrogens), chemotherapy, or herbal medications administered with the intent to treat the patient's malignancy

* Patients on valproic acid (a histone-deacetylase inhibitor) to treat prostate cancer are not eligible
* History of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would compromise compliance with study requirements
* Currently active secondary malignancy (as determined by the treating physician) other than non-melanoma skin cancer

Minimum Eligible Age

19 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susan Slovin

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

UMDNJ - New Jersey Medical School

Newark, New Jersey, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Countries

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United States