Clinical trial NCT00106691: Prostate Cancer Prevention Study for Men With High Grade PIN (Prostatic Intraepithelial Neoplasia)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Efficacy and Safety Study of Toremifene Citrate for the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia (PIN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preneoplastic Conditions
Prostatic Intraepithelial Neoplasia
Keywords: neoplasia
chemoprevention
cancer
premalignant
precancerous
Chemoprophylaxis
Intraepithelial Prostatic Neoplasia
Neoplasia, Prostatic Intraepithelial
Lead sponsor: GTx
Sponsor class: INDUSTRY
First posted: 2005-03-30
Enrollment: 1589
Sex: MALE
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if toremifene citrate is effective and safe in the prevention of prostate cancer in men who have been diagnosed with high grade prostatic intraepithelial neoplasia (PIN).

Detailed description: The purpose of this study is to determine if toremifene citrate is effective and safe in the prevention of prostate cancer in men who have been diagnosed with high grade prostatic intraepithelial neoplasia. Men who have ever been diagnosed with high grade PIN will be enrolled into an 36 month trial and will be assigned to either 20 mg of study drug or placebo per day. Subjects will undergo safety evaluations at Month 3, Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 along with prostate biopsies at Month 12 and Month 24 and Month 36 to determine efficacy.

Eligibility criteria: Inclusion Criteria:

* Give voluntary signed informed consent in accordance with institutional policies
* Be male, aged ≥ 30 years
* Have a diagnosis of high grade PIN from any previous prostate biopsy. The diagnosis of high grade PIN must be confirmed by the central pathologist
* Have had a prostate biopsy in the last 6 months with a minimum of 10 cores that shows no evidence of cancer as confirmed by the central pathologist; OR, have had 2 prostate biopsies (each with a minimum of 6 cores) in the 12 months prior to screening with at least one of the biopsies occurring within 6 months prior to the screening visit. Both biopsies should have no evidence of cancer as confirmed by the central pathologist
* Have a serum PSA of ≤ 10 ng/mL
* Agree to provide tablet containers for tablet counts and to complete a daily diary of study drug intake
* Agree to use an effective method of contraception, if the partner is of child-bearing age, while on study and for 30 days after the last dose of study medication
* Have adequate bone marrow, liver and renal function:

  * White Blood Cell (WBC) Count ≥ 3,000/mm3;
  * Platelet Count ≥ 100,000/mm3;
  * Bilirubin ≤ 1.5 mg/dL;
  * AST and ALT \< 2x upper limit of normal;
  * Serum Creatinine ≤ 2.0 mg%

Exclusion Criteria:

* Previous exposure to toremifene citrate
* Have evidence of prostate cancer (local, regional and/or distal metastasis)
* Have any history of other malignancies (Exceptions include non-melanoma skin cancer or other cancer that has no evidence of tumor reoccurrence 5 years after definitive treatment).
* Have active systemic viral, bacterial, or fungal infections requiring treatment
* Have, in the judgment of the investigator, a clinically significant concurrent illness or psychological, familial, sociological, geographical or other concomitant condition that would not permit adequate follow-up and compliance with the study protocol
* Concurrently being treated with other investigational agents or have participated in an investigational study within 60 days prior to screening
* Currently taking dutasteride. Subject is eligible if he stops dutasteride for a total washout of 90 days prior to the Screening Visit and agrees not to use dutasteride for the duration of the study.
* Have previously taken finasteride for greater than two years
* Currently taking finasteride. Subject is eligible if he stops finasteride for a total washout of 30 days prior to the Screening Visit and agrees not to use finasteride for the duration of the study.
* Currently taking testosterone or testosterone-like supplements, such as dehydroepiandrosterone (DHEA). Subject is eligible if he stops these agents for a total washout of 30 days prior to the Screening Visit and agrees not to use these agents for the duration of the study.
* Have a history of taking PC-SPES within the past two years.
* Currently taking herbal medicine or dietary supplements for prostate health, such as Saw Palmetto (also known as Serenoa Repens).

Subject is eligible if he stops these agents for a total washout of 30 days prior to taking the first dose of study drug and agrees not to use these agents for the duration of the study.

Lycopene, vitamin E and selenium are not prohibited and no washout is required. However, vitamin E intake should be limited to less than 400 i.u. per day.

* Have a history of thromboembolic event or disease including deep vein thrombosis, pulmonary embolus, or thrombotic stroke
* History of chronic hepatitis or cirrhosis

Primary outcomes:
measure: Efficacy of Toremifene in the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia (PIN)
timeFrame: The outcome measurement time is up to 36 months
measure: Occurrence of a Positive Cancer Biopsy
timeFrame: Up to 36 months
Secondary outcomes:
measure: The Effect of Toremifene on Lipid Levels
timeFrame: Up to 36 months
measure: The Effect of Toremifene on Hormone Levels
timeFrame: Up to 36 months
measure: The Effect of Toremifene on Total PSA (Prostate Specific Antigen) Levels
timeFrame: Up to 36 months
measure: The Effect of Toremifene on the Mean Change at 36 Months in AUA (American Urological Association) Symptom Score
timeFrame: 36 months
measure: Occurrence of High Grade PIN at the 12, 24, 36 Month Biopsies
timeFrame: Up to 36 months
measure: The Effect of Toremifene on % Free Serum PSA (Prostate Specific Antigen) Levels, Change From Baseline
timeFrame: 36 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Medical Affiliated Research Ctr.
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Phoenix
country: United States
facility: Hope Research Inst.
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: San Bernardino
country: United States
facility: San Bernardino Urological Associates Medical Group
state: California
city: Torrance
country: United States
facility: Western Clinical Research, Inc.
state: California
city: Aurora
country: United States
facility: Urology Research Options
state: Colorado
city: Denver
country: United States
facility: Urology Associates, P.C.
state: Colorado
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Surgical Group
state: Connecticut
city: Trumbull
country: United States
facility: Urological Associates of Bridgeport
state: Connecticut
city: Waterbury
country: United States
facility: Connecticut Clinical Research
state: Connecticut
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Daytona Beach
country: United States
facility: Atlantic Urological Associates
state: Florida
city: Fort Myers
country: United States
facility: Southwest Florida Urologic Associates
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute
state: Florida
city: Ocala
country: United States
facility: UroSearch
state: Florida
city: Ocala
country: United States
facility: Central Florida Urology Group/ UroSearch
state: Florida
city: Ocala
country: United States
facility: Florida Foundation for Healthcare Research
state: Florida
city: Orlando
country: United States
facility: Winter Park Urology Associates
state: Florida
city: Panama City
country: United States
facility: Panama City Urological Center
state: Florida
city: Pembroke Pines
country: United States
facility: Demaur Clinical Research Center
state: Florida
city: Pinellas Park
country: United States
facility: DMI Research
state: Florida
city: Pinellas Park
country: United States
facility: Urology Consultants
state: Florida
city: Sarasota
country: United States
facility: Florida Urology Specialists
state: Florida
city: Atlanta
country: United States
facility: Midtown Urology
state: Georgia
city: Atlanta
country: United States
facility: Georgia Urology
state: Georgia
city: Marietta
country: United States
facility: Urology Enterprises
state: Georgia
city: Roswell
country: United States
facility: North Fulton Urology
state: Georgia
city: Savannah
country: United States
facility: St. Joseph's, Candler Health System
state: Georgia
city: Peoria
country: United States
facility: Specialty Care Research
state: Illinois
city: Indianapolis
country: United States
facility: Urology of Indiana, LLC
state: Indiana
city: Jeffersonville
country: United States
facility: Metropolitan Urology, PSC
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Urology Care, P.C.
state: Kansas
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Urology
state: Maryland
city: Baltimore
country: United States
facility: Maryland Prostate Center: University of Maryland Medical Center
state: Maryland
city: Greenbelt
country: United States
facility: Drs. Werner, Murdock, & Francis PA, Urology Associates
state: Maryland
city: Hagerstown
country: United States
facility: Urology Center, PA
state: Maryland
city: Rockville
country: United States
facility: Mid Atlantic Clinical Research
state: Maryland
city: Towson
country: United States
facility: Chesapeake Urology Research Assoc.
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital, Division of Urological Surgery
state: Massachusetts
city: Brighton
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Grand Rapids
country: United States
facility: Michigan Medical, PC Urology
state: Michigan
city: Saint Clair Shores
country: United States
facility: Mich. Inst. of Urology
state: Michigan
city: Sartell
country: United States
facility: Adult & Pediatric Urology
state: Minnesota
city: Chesterfield
country: United States
facility: St. Louis Urological Surgeons
state: Missouri
city: Florissant
country: United States
facility: Metropolitan Urological Specialists
state: Missouri
city: Independence
country: United States
facility: Midwest Urology Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Urologic Research Ctr.
state: Missouri
city: Lincoln
country: United States
facility: Urology PC
state: Nebraska
city: Las Vegas
country: United States
facility: Sheldon Freeman
state: Nevada
city: Reno
country: United States
facility: Urologic Surgeons, Ltd.
state: Nevada
city: Brick
country: United States
facility: Coastal Urology Associates
state: New Jersey
city: Edison
country: United States
facility: Central Jersey Clinical Research
state: New Jersey
city: Hamilton
country: United States
facility: Hamilton Urology PA
state: New Jersey
city: Marlton
country: United States
facility: Delaware Valley Urology
state: New Jersey
city: Mount Laurel
country: United States
facility: Delaware Valley Urology
state: New Jersey
city: Albuquerque
country: United States
facility: Urology Group of New Mexico
state: New Mexico
city: Albany
country: United States
facility: The Urological Institute of Northeastern Research Department
state: New York
city: Elmont
country: United States
facility: Metropolitan Urologic Services, P.C.
state: New York
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: Garden City
country: United States
facility: Urological Surgeons of Long Island
state: New York
city: Lake Success
country: United States
facility: Lake Success Urological Associates
state: New York
city: Manhasset
country: United States
facility: Urology Associates, PC
state: New York
city: New York
country: United States
facility: NYU Urology Associates
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Oneida
country: United States
facility: CNY Urology
state: New York
city: Staten Island
country: United States
facility: Staten Island Urological Research
state: New York
city: Asheboro
country: United States
facility: Asheboro Urology Clinic
state: North Carolina
city: Charlotte
country: United States
facility: McKay Urology
state: North Carolina
city: Raleigh
country: United States
facility: Wake Urology Associates
state: North Carolina
city: Akron
country: United States
facility: Summa Health System, Cancer Research Office
state: Ohio
city: Cincinnati
country: United States
facility: Tri-State Urologic Services/PSC, Inc. d/b/a The Urology Group
state: Ohio
city: Columbus
country: United States
facility: Capital Urology
state: Ohio
city: Columbus
country: United States
facility: Columbus Urology, Inc.
state: Ohio
city: Elyria
country: United States
facility: Urology of Northern Ohio
state: Ohio
city: Middleburg Heights
country: United States
facility: Southwest Urology
state: Ohio
city: Bethany
country: United States
facility: Parkhurst Research Organization
state: Oklahoma
city: Tulsa
country: United States
facility: Urologic Specialists of Oklahoma Research Department
state: Oklahoma
city: Springfield
country: United States
facility: Oregon Urology Specialists
state: Oregon
city: Allentown
country: United States
facility: Urologic Associates of Allentown
state: Pennsylvania
city: Bala-Cynwyd
country: United States
facility: Urologic Surgery, P.C.
state: Pennsylvania
city: Lancaster
country: United States
facility: Urological Associates of Lancaster, Ltd.
state: Pennsylvania
city: Monroeville
country: United States
facility: The Urology Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Triangle Urological Group
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Department of Urology
state: Pennsylvania
city: State College
country: United States
facility: State College Urologic Associates, Inc.
state: Pennsylvania
city: Providence
country: United States
facility: University Urological Research Institute
state: Rhode Island
city: Columbia
country: United States
facility: Columbia Urological Associates
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Germantown
country: United States
facility: Urology Center of the South
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Memphis
country: United States
facility: Southeast Urology Network
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee, Dept. of Urology
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Austin
country: United States
facility: Professional Quality Research
state: Texas
city: Dallas
country: United States
facility: Research Across America
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research, PA
state: Texas
city: Salt Lake City
country: United States
facility: Advanced Clinical Research
state: Utah
city: Salt Lake City
country: United States
facility: Salt Lake Research
state: Utah
city: Norfolk
country: United States
facility: Devine-Tidewater Urology
state: Virginia
city: Richmond
country: United States
facility: Med Atlantic, Inc (Virginia Urology)
state: Virginia
city: Seattle
country: United States
facility: Seattle Urological Associates
state: Washington
city: Spokane
country: United States
facility: Deaconess Medical Center
state: Washington
city: Tacoma
country: United States
facility: Urologic Northwest Surgeons
state: Washington
city: Tacoma
country: United States
facility: Urology Services Madigan Army Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Centro Urologico Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Pirovano
city: Buenos Aires
country: Argentina
facility: Policlinico Bancario de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Sanatorio Municipal
city: Buenos Aires
country: Argentina
facility: Servicio de Urologia
city: Calgary
country: Canada
facility: Prostate Cancer Inst.
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Urology Inst.. Research Center
state: Alberta
city: Kelowna
country: Canada
facility: Southern Interior Medical Research Inc.
state: British Columbia
city: Victoria
country: Canada
facility: Dr. G. Steinhoff Clinical Research
state: British Columbia
city: Fredericton
country: Canada
facility: Allan B. Patrick, M.D. Professional corporation
state: New Brunswick
city: Halifax
country: Canada
facility: Queen Elizabeth Health Sciences Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Male/Female Health and Research Centre
state: Ontario
city: Burlington
country: Canada
facility: Burlington Urology
state: Ontario
city: Kingston
country: Canada
facility: Centre for Advanced Urological Research
state: Ontario
city: Kitchener
country: Canada
facility: Urology Assoc./Urologic Medical Research
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Mor Urology
state: Ontario
city: Oakville
country: Canada
facility: The Fe/Male Health Centres
state: Ontario
city: Oshawa
country: Canada
facility: Urotec
state: Ontario
city: Toronto
country: Canada
facility: The Health Institute for Men
state: Ontario
city: Toronto
country: Canada
facility: Stanley Flax Medical Professional Corp.
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network, Princess Margaret Hospital Prostate Centre
state: Ontario
city: Toronto
country: Canada
facility: The Male Health Centre
state: Ontario
city: Willowdale
country: Canada
facility: Roger Buckley, MD
state: Ontario
city: Greenfield Park
country: Canada
facility: Urology South Shore Research
state: Quebec
city: Montreal
country: Canada
facility: Les Urologues Associes du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill Urology Associates
state: Quebec
city: Pointe Claire
country: Canada
facility: Ultra-Med, Inc.
state: Quebec
city: Trois-Rivieres
country: Canada
facility: G.R.U.M.
state: Quebec
Study officials:
affiliation: NYU Langone Medical Center
name: Samir Taneja, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taneja SS, Morton R, Barnette G, Sieber P, Hancock ML, Steiner M. Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene. J Clin Oncol. 2013 Feb 10;31(5):523-9. doi: 10.1200/JCO.2012.41.7634. Epub 2013 Jan 7.