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: April 9, 2014
Last verified: December 2013

December 20, 2007
April 9, 2014
November 2007
April 2015   (final data collection date for primary outcome measure)
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%).
Pathologic complete response at 12 weeks [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00589472 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Not Provided
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
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Prostate
  • Stage I Prostate Cancer
  • Stage IIA Prostate Cancer
  • Stage IIB Prostate Cancer
  • Stage III Prostate Cancer
  • 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
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: leuprolide acetate
  • Drug: goserelin acetate
  • Drug: vorinostat
  • Procedure: therapeutic conventional surgery
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
38
Not Provided
April 2015   (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
Male
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00589472
NCI-2009-00238, NCI-2009-00238, MSKCC IRB 06-160, MSKCC-06160, CDR0000579559, 06-160, 7864, N01CM62206, N01CM62205, P30CA008748
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Susan Slovin Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
December 2013

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