Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer (TARGET)
|Prostate Adenocarcinoma Stage I Prostate Cancer Stage IIA Prostate Cancer Stage IIB Prostate Cancer Stage III Prostate Cancer||Drug: Bicalutamide Drug: Goserelin Acetate Other: Laboratory Biomarker Analysis Drug: Leuprolide Acetate Procedure: Therapeutic Conventional Surgery Drug: Vorinostat||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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)|
- 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.
- 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 ]
- 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 ]
|Study Start Date:||November 2007|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
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.
Other Names:Drug: Goserelin Acetate
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Leuprolide Acetate
Other Names:Procedure: Therapeutic Conventional Surgery
Undergo radical prostatectomyDrug: Vorinostat
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.
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.
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00589472
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00589472
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|UCSF Medical Center-Parnassus|
|San Francisco, California, United States, 94143|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel 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 Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New Jersey|
|UMDNJ - New Jersey Medical School|
|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|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Susan Slovin||Memorial Sloan Kettering Cancer Center|