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

NCT00589472 | Completed Phase 2 Results DMC

• 9 other identifiers: NCI-2009-0023806-160MSKCC IRB 06-160MSKCC-06160CDR00005795597864N01CM62205N01CM62206P30CA008748
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response at the Time of Surgery

  The primary endpoint will be pathologic complete response at the time of surgery. This represents the proportion of patients with no evidence of disease in the prostate (ie, the absence of tumor in the posttherapy pathology specimen) at the time of radical prostatectomy. Pathologic complete response at the time of surgery is the primary endpoint for this study. 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 12 weeks (Type I error 10% and power 90%). A maximum of 38 pts were planned for accrual onto this study. If zero or one response was observed, then the trial was to be stopped. The design had power 0.90 for a population response proportion to 0.20 using a one-sided 0.10 size test. pT2 indicates that the cancer is confined to the prostate, while pT3 indicates that there is an extraprostatic extension of the cancer.

  At 12 weeks

Secondary Outcomes (6)

• Gleason Score

  Baseline

• Levels of DHEA in Blood From Radical Prostatectomy Specimens

  Up to 1 year

• Levels of DHEA-S in Blood From Radical Prostatectomy Specimens

  Up to 1 year

• Levels of DHT in Blood From Radical Prostatectomy Specimens

  Up to 1 year

• Levels of PSA in Blood From Radical Prostatectomy Specimens

  Up to 1 year

Other Outcomes (10)

• Protein Expression Analysis, Including AR Target Genes, PSA and TMPRSS2

  Up to 1 year

• Safety and Tolerability of Androgen Depletion Therapy in Combination With Vorinostat as Assessed by Physical Examinations, Adverse Events, and Laboratory Assessments. Please See Adverse Events Section.

  Up to 1 year

• Gene Expression Analysis, Including AR Target Genes, PSA and TMPRSS2

  at 12 weeks

Study Arms (1)

Treatment (Antihormone therapy and enzyme inhibitor therapy)

EXPERIMENTAL

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; Drug: Goserelin Acetate; Other: Laboratory Biomarker Analysis; Drug: Leuprolide Acetate; Procedure: Therapeutic Conventional Surgery; Drug: Vorinostat

Interventions

Bicalutamide DRUG

Given PO

Also known as: Casodex, Cosudex, ICI 176,334, ICI 176334

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Goserelin Acetate DRUG

Given SC

Also known as: ZDX, Zoladex

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Leuprolide Acetate DRUG

Given IM

Also known as: 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

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Therapeutic Conventional Surgery PROCEDURE

Undergo radical prostatectomy

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (15)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

UMDNJ - New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide; Goserelin; Leuprolide; luprolide acetate gel depot; Vorinostat

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Dr. Susan Slovin
• Organization: Memorial Sloan Kettering Cancer Center

slovins@mskcc.org

646-422-4470

Study Officials

• Susan Slovin

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: January 9, 2008
• Study Start: November 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: October 6, 2017
• Results First Posted: October 6, 2017

Record last verified: 2017-09

Locations

US (15)