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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00589472
First Posted: January 9, 2008
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
December 20, 2007
January 9, 2008
March 24, 2017
October 6, 2017
October 6, 2017
November 2007
June 2010   (Final data collection date for primary outcome measure)
Pathologic Complete Response at the Time of Surgery [ Time Frame: At 12 weeks ]
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.
Pathologic complete response at 12 weeks
Complete list of historical versions of study NCT00589472 on ClinicalTrials.gov Archive Site
  • Gleason Score [ Time Frame: Baseline ]
    A Gleason score is the sum of two numbers. Pathologist determines where the cancer is most prominent and assigns the primary grade, the secondary grade is assigned based on where the cancer is next most prominent. A score from one to five is assigned for each area based on how aggressive the tumor appears. A tumor with cell that appear close to normal is assigned a low Gleason score (six or below). A tumor with cells that appear clearly different from those of a normal prostate is assigned a high Gleason score (seven or above). A system of grading prostate cancer tissue based on how it looks under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer tissue is similar to normal prostate tissue and the tumor is less likely to spread; a high Gleason score means the cancer tissue is very different from normal and the tumor is more likely to spread.
  • Levels of DHEA in Blood From Radical Prostatectomy Specimens [ Time Frame: Up to 1 year ]
  • Levels of DHEA-S in Blood From Radical Prostatectomy Specimens [ Time Frame: Up to 1 year ]
  • Levels of DHT in Blood From Radical Prostatectomy Specimens [ Time Frame: Up to 1 year ]
  • Levels of PSA in Blood From Radical Prostatectomy Specimens [ Time Frame: Up to 1 year ]
  • Levels of Testosterone in Blood From Radical Prostatectomy Specimens [ Time Frame: Up to 1 year ]
  • Pre- and post-treatment levels of PSA, testosterone, DHT, DHEA, and DHEA-S in blood and radical prostatectomy specimens
  • Pre- and post-treatment levels of testosterone, androstenedione, androstenediol, DHT, DHEA, and DHEA-S in prostate tissue
  • 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
  • Exploratory gene microarray analysis
  • Safety and tolerability of androgen depletion therapy in combination with vorinostat (SAHA) as assessed by physical examinations, adverse events, and laboratory assessments
  • Protein Expression Analysis, Including AR Target Genes, PSA and TMPRSS2 [ Time Frame: 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. [ Time Frame: Up to 1 year ]
    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.
  • Gene Expression Analysis, Including AR Target Genes, PSA and TMPRSS2 [ Time Frame: at 12 weeks ]
    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 ]
  • Levels of Testosterone in Prostate Tissue [ Time Frame: Up to 1 year ]
  • Levels of DHT in Prostate Tissue [ Time Frame: Up to 1 year ]
  • Levels of Androstenediol in Prostate Tissue [ Time Frame: Up to 1 year ]
  • Levels of Androstenedione in Prostate Tissue [ Time Frame: Up to 1 year ]
  • Levels of DHEA in Prostate Tissue [ Time Frame: Up to 1 year ]
  • Levels of DHEA-S in Prostate Tissue [ Time Frame: Up to 1 year ]
Not Provided
 
Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer
Neoadjuvant Androgen Depletion in Combination With Vorinostat Followed by Radical Prostatectomy for Localized Prostate Cancer: Total Androgen-Receptor Gene Expression Targeted Therapy (TARGET)
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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Prostate Adenocarcinoma
  • Stage I Prostate Cancer
  • Stage IIA Prostate Cancer
  • Stage IIB Prostate Cancer
  • Stage III Prostate Cancer
  • Drug: Bicalutamide
    Given PO
    Other Names:
    • Casodex
    • Cosudex
    • ICI 176,334
    • ICI 176334
  • Drug: Goserelin Acetate
    Given SC
    Other Names:
    • ZDX
    • Zoladex
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Leuprolide Acetate
    Given IM
    Other Names:
    • 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
  • Procedure: Therapeutic Conventional Surgery
    Undergo radical prostatectomy
  • Drug: Vorinostat
    Given PO
    Other Names:
    • L-001079038
    • SAHA
    • Suberanilohydroxamic Acid
    • Suberoylanilide Hydroxamic Acid
    • Zolinza
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.
Interventions:
  • Drug: Bicalutamide
  • Drug: Goserelin Acetate
  • Other: Laboratory Biomarker Analysis
  • Drug: Leuprolide Acetate
  • Procedure: Therapeutic Conventional Surgery
  • Drug: Vorinostat
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
June 2010
June 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: Male
19 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
Canada
 
NCT00589472
NCI-2009-00238
NCI-2009-00238 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
06-160
MSKCC IRB 06-160
MSKCC-06160
CDR0000579559
06-160 ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
7864 ( Other Identifier: CTEP )
N01CM62205 ( U.S. NIH Grant/Contract )
N01CM62206 ( U.S. NIH Grant/Contract )
P30CA008748 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Susan Slovin Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP