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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00589472
First received: December 20, 2007
Last updated: September 16, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Prostate
Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Drug: bicalutamide
Drug: leuprolide acetate
Drug: goserelin acetate
Drug: vorinostat
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Pathologic complete response at the time of surgery [ Time Frame: At 12 weeks ] [ Designated as safety issue: No ]
    A Simon 2-stage optimal design that differentiates between response probabilities of 0.05 and 0.20 will be used in the analysis of the pathological complete response at the time of surgery (Type I error 10% and power 90%).


Secondary Outcome Measures:
  • Levels of PSA in blood from radical prostatectomy specimens [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of testosterone in blood from radical prostatectomy specimens [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of DHT in blood from radical prostatectomy specimens [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of DHEA in blood from radical prostatectomy specimens [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of DHEA-S in blood from radical prostatectomy specimens [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of testosterone in prostate tissue [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of androstenedione in prostate tissue [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of androstenediol in prostate tissue [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of DHT in prostate tissue [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of DHEA in prostate tissue [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Levels of DHEA-S in prostate tissue [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Gene expression analysis, including AR target genes, PSA and TMPRSS2 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Estimates and 95% confidence intervals for the proportion of patients with nondetectable levels of PSA and TMPRSS2 will be computed.

  • Protein expression analysis, including AR target genes, PSA and TMPRSS2 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Estimates and 95% confidence intervals for the proportion of patients with nondetectable levels of PSA and TMPRSS2 will be computed.

  • Gene microarray analysis [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Safety and tolerability of androgen depletion therapy in combination with vorinostat as assessed by physical examinations, adverse events, and laboratory assessments [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    Adverse events will be monitored at each scheduled visit and throughout the study. Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.


Estimated Enrollment: 38
Study Start Date: November 2007
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: bicalutamide
Given PO
Other Names:
  • Casodex
  • CDX
Drug: leuprolide acetate
Given IM
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
Drug: goserelin acetate
Given SC
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Procedure: therapeutic conventional surgery
Undergo radical prostatectomy
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
University of California at Los Angeles (UCLA )
Los Angeles, California, United States, 90095
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
University of Medicine and Dentistry (Minority-Based CCOP)
Newark, New Jersey, United States, 07103
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
Canada, British Columbia
Vancouver General Hospital-Heather Pavilion
Vancouver, British Columbia, Canada, V5Z-3J5
Sponsors and Collaborators
Investigators
Principal Investigator: Susan Slovin Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00589472     History of Changes
Other Study ID Numbers: NCI-2009-00238, NCI-2009-00238, MSKCC IRB 06-160, MSKCC-06160, CDR0000579559, 06-160, 7864, P30CA008748, N01CM62205, N01CM62206
Study First Received: December 20, 2007
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Androgens
Vorinostat
Bicalutamide
Leuprolide
Goserelin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Androgen Antagonists

ClinicalTrials.gov processed this record on September 18, 2014