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

Primary Purpose

Prostate Adenocarcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bicalutamide
Goserelin Acetate
Laboratory Biomarker Analysis
Leuprolide Acetate
Therapeutic Conventional Surgery
Vorinostat
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Adenocarcinoma

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA / Jonsson Comprehensive Cancer Center
  • UCSF Medical Center-Parnassus
  • University of Chicago Comprehensive Cancer Center
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Wayne State University/Karmanos Cancer Institute
  • Mayo Clinic
  • UMDNJ - New Jersey Medical School
  • Memorial Sloan-Kettering Cancer Center
  • Duke University Medical Center
  • Oregon Health and Science University
  • M D Anderson Cancer Center
  • University of Washington Medical Center
  • University of Wisconsin Hospital and Clinics

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (Antihormone therapy and enzyme inhibitor therapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Gleason Score
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
Levels of DHEA-S in Blood From Radical Prostatectomy Specimens
Levels of DHT in Blood From Radical Prostatectomy Specimens
Levels of PSA in Blood From Radical Prostatectomy Specimens
Levels of Testosterone in Blood From Radical Prostatectomy Specimens

Full Information

First Posted
December 20, 2007
Last Updated
September 18, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00589472
Brief Title
Androgen Deprivation Therapy and Vorinostat Followed by Radical Prostatectomy in Treating Patients With Localized Prostate Cancer
Acronym
TARGET
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Adenocarcinoma, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (Antihormone therapy and enzyme inhibitor therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bicalutamide
Other Intervention Name(s)
Casodex, Cosudex, ICI 176,334, ICI 176334
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Goserelin Acetate
Other Intervention Name(s)
ZDX, Zoladex
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Leuprolide Acetate
Other Intervention Name(s)
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
Intervention Description
Given IM
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo radical prostatectomy
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Pathologic Complete Response at the Time of Surgery
Description
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.
Time Frame
At 12 weeks
Secondary Outcome Measure Information:
Title
Gleason Score
Description
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.
Time Frame
Baseline
Title
Levels of DHEA in Blood From Radical Prostatectomy Specimens
Time Frame
Up to 1 year
Title
Levels of DHEA-S in Blood From Radical Prostatectomy Specimens
Time Frame
Up to 1 year
Title
Levels of DHT in Blood From Radical Prostatectomy Specimens
Time Frame
Up to 1 year
Title
Levels of PSA in Blood From Radical Prostatectomy Specimens
Time Frame
Up to 1 year
Title
Levels of Testosterone in Blood From Radical Prostatectomy Specimens
Time Frame
Up to 1 year
Other Pre-specified Outcome Measures:
Title
Protein Expression Analysis, Including AR Target Genes, PSA and TMPRSS2
Time Frame
Up to 1 year
Title
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.
Description
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.
Time Frame
Up to 1 year
Title
Gene Expression Analysis, Including AR Target Genes, PSA and TMPRSS2
Description
Estimates and 95% confidence intervals for the proportion of patients with nondetectable levels of PSA and TMPRSS2 will be computed.
Time Frame
at 12 weeks
Title
Gene Microarray Analysis
Time Frame
Up to 1 year
Title
Levels of Testosterone in Prostate Tissue
Time Frame
Up to 1 year
Title
Levels of DHT in Prostate Tissue
Time Frame
Up to 1 year
Title
Levels of Androstenediol in Prostate Tissue
Time Frame
Up to 1 year
Title
Levels of Androstenedione in Prostate Tissue
Time Frame
Up to 1 year
Title
Levels of DHEA in Prostate Tissue
Time Frame
Up to 1 year
Title
Levels of DHEA-S in Prostate Tissue
Time Frame
Up to 1 year

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Slovin
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA / Jonsson Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSF Medical Center-Parnassus
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Chicago Comprehensive Cancer Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
UMDNJ - New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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