Prostate Cancer Prevention Study for Men With High Grade PIN (Prostatic Intraepithelial Neoplasia)

Phase 3

Completed

Conditions: Preneoplastic Conditions
Prostatic Intraepithelial Neoplasia

Interventions: Drug: Toremifene 20 mg
Drug: Placebo

Registration Number: NCT00106691

Lead Sponsor: GTx

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 1589

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
20 mg Toremifene Citrate	Toremifene 20 mg	The subject takes one dose by mouth of the 20mg Toremifine Citrate tablet once a day for the length of the trial (360 days).
Placebo	Placebo	The subject takes a placebo tablet identical in appearance to the toremifene 20mg tablet, administered by mouth daily for 360 days

Primary Outcome Measures

Name	Time	Method
Efficacy of Toremifene in the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia (PIN)	The outcome measurement time is up to 36 months	To measure the efficacy of toremifene citrate in men with high grade prostatic intraepithelial neoplasia (PIN). Prostate cancer-free survival distributions (Kaplan-Meier)
Occurrence of a Positive Cancer Biopsy	Up to 36 months	To measure the occurrence of a positive cancer biopsy

Secondary Outcome Measures

Name	Time	Method
The Effect of Toremifene on % Free Serum PSA (Prostate Specific Antigen) Levels, Change From Baseline	36 months	To assess the effect of toremifene in % free serum PSA (prostate specific antigen) levels, change from baseline
The Effect of Toremifene on Lipid Levels	Up to 36 months	Measure lipid levels including total cholesterol, LDL, HDL and Triglycerides % change from baseline
The Effect of Toremifene on Hormone Levels	Up to 36 months	% Change from baseline hormone levels, including total testosterone, free testosterone, dihydrotestosterone (DHT) and estradiol
The Effect of Toremifene on Total PSA (Prostate Specific Antigen) Levels	Up to 36 months	To assess the effect of toremifene in the total PSA (prostate specific antigen) levels from baseline
The Effect of Toremifene on the Mean Change at 36 Months in AUA (American Urological Association) Symptom Score	36 months	To assess the effect of toremifene on the AUA (American Urological Association) symptom score mean change from baseline. Scores of 0-7=mild severity, 8-9, moderate, and 20-30, severe with possible responses of 0 (not at all) 1 (\<1/5), 2 (\<50% time), 3 (about 50% time), 4 (\> 50% time) \& 5 (Almost Always). There are 7 questions (1)Incomplete emptying (2)Frequency (3)Intermittency (4)Urgency (5)Weak-stream (6)Straining \& (7)Nocturia. Analysis is change from baseline at final evaluation (36 months) for quality of life due to urinary symptoms. The P Value is from a Wilcoxon signed-rank test. Scores can range from 0-35, highest representing worse symptoms
Occurrence of High Grade PIN at the 12, 24, 36 Month Biopsies	Up to 36 months	To measure the occurrence of high grade PIN at the 12, 24, 36 Month intervals in the 360 days study.

Trial Locations

Locations (137): Chesapeake Urology Research Assoc.
🇺🇸
Towson, Maryland, United States
The Male Health Centre
🇨🇦
Toronto, Ontario, Canada
Stanley Flax Medical Professional Corp.
🇨🇦
Toronto, Ontario, Canada
Urology Center, PA
🇺🇸
Hagerstown, Maryland, United States
Triangle Urological Group
🇺🇸
Pittsburgh, Pennsylvania, United States
Seattle Urological Associates
🇺🇸
Seattle, Washington, United States
Tri-State Urologic Services/PSC, Inc. d/b/a The Urology Group
🇺🇸
Cincinnati, Ohio, United States
Connecticut Clinical Research
🇺🇸
Waterbury, Connecticut, United States
Arkansas Urology
🇺🇸
Little Rock, Arkansas, United States
Connecticut Surgical Group
🇺🇸
Hartford, Connecticut, United States
Hospital Pirovano
🇦🇷
Buenos Aires, Argentina
Dr. G. Steinhoff Clinical Research
🇨🇦
Victoria, British Columbia, Canada
Urological Associates of Bridgeport
🇺🇸
Trumbull, Connecticut, United States
Prostate Cancer Inst.
🇨🇦
Calgary, Alberta, Canada
G.R.U.M.
🇨🇦
Trois-Rivieres, Quebec, Canada
Hospital Italiano de Buenos Aires
🇦🇷
Buenos Aires, Argentina
Servicio de Urologia
🇦🇷
Buenos Aires, Argentina
Policlinico Bancario de Buenos Aires
🇦🇷
Buenos Aires, Argentina
Ultra-Med, Inc.
🇨🇦
Pointe Claire, Quebec, Canada
Allan B. Patrick, M.D. Professional corporation
🇨🇦
Fredericton, New Brunswick, Canada
Hope Research Inst.
🇺🇸
Phoenix, Arizona, United States
Urology Associates, P.C.
🇺🇸
Denver, Colorado, United States
The Urology Center of Colorado
🇺🇸
Denver, Colorado, United States
Urology Associates
🇺🇸
Nashville, Tennessee, United States
Advanced Clinical Research
🇺🇸
Salt Lake City, Utah, United States
Salt Lake Research
🇺🇸
Salt Lake City, Utah, United States
Urology Group of New Mexico
🇺🇸
Albuquerque, New Mexico, United States
Coastal Urology Associates
🇺🇸
Brick, New Jersey, United States
Hamilton Urology PA
🇺🇸
Hamilton, New Jersey, United States
Metropolitan Urologic Services, P.C.
🇺🇸
Elmont, New York, United States
Sheldon Freeman
🇺🇸
Las Vegas, Nevada, United States
Florida Foundation for Healthcare Research
🇺🇸
Ocala, Florida, United States
Adult & Pediatric Urology
🇺🇸
Sartell, Minnesota, United States
DMI Research
🇺🇸
Pinellas Park, Florida, United States
Urology PC
🇺🇸
Lincoln, Nebraska, United States
Central Jersey Clinical Research
🇺🇸
Edison, New Jersey, United States
Georgia Urology
🇺🇸
Atlanta, Georgia, United States
Florida Urology Specialists
🇺🇸
Sarasota, Florida, United States
UroSearch
🇺🇸
Ocala, Florida, United States
Urology Consultants
🇺🇸
Pinellas Park, Florida, United States
Midtown Urology
🇺🇸
Atlanta, Georgia, United States
Central Florida Urology Group/ UroSearch
🇺🇸
Ocala, Florida, United States
Kansas City Urology Care, P.C.
🇺🇸
Overland Park, Kansas, United States
Maryland Prostate Center: University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
Brigham & Women's Hospital, Division of Urological Surgery
🇺🇸
Boston, Massachusetts, United States
Regional Urology, LLC
🇺🇸
Shreveport, Louisiana, United States
Boston Clinical Trials
🇺🇸
Brighton, Massachusetts, United States
Washington University Urologic Research Ctr.
🇺🇸
Saint Louis, Missouri, United States
Drs. Werner, Murdock, & Francis PA, Urology Associates
🇺🇸
Greenbelt, Maryland, United States
Metropolitan Urological Specialists
🇺🇸
Florissant, Missouri, United States
Midwest Urology Center
🇺🇸
Independence, Missouri, United States
St. Louis Urological Surgeons
🇺🇸
Chesterfield, Missouri, United States
Urological Associates of Lancaster, Ltd.
🇺🇸
Lancaster, Pennsylvania, United States
Centro Urologico Buenos Aires
🇦🇷
Buenos Aires, Argentina
Delaware Valley Urology
🇺🇸
Mount Laurel, New Jersey, United States
Urological Surgeons of Long Island
🇺🇸
Garden City, New York, United States
Southwest Urology
🇺🇸
Middleburg Heights, Ohio, United States
Urologic Surgery, P.C.
🇺🇸
Bala-Cynwyd, Pennsylvania, United States
Capital Urology
🇺🇸
Columbus, Ohio, United States
Urology Center of the South
🇺🇸
Germantown, Tennessee, United States
Urologic Associates of Allentown
🇺🇸
Allentown, Pennsylvania, United States
Staten Island Urological Research
🇺🇸
Staten Island, New York, United States
AccuMed Research Associates
🇺🇸
Garden City, New York, United States
CNY Urology
🇺🇸
Oneida, New York, United States
Urologic Northwest Surgeons
🇺🇸
Tacoma, Washington, United States
Southeast Urology Network
🇺🇸
Memphis, Tennessee, United States
Queen Elizabeth Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada
Volunteer Research Group
🇺🇸
Knoxville, Tennessee, United States
Oregon Urology Specialists
🇺🇸
Springfield, Oregon, United States
The Urology Institute
🇺🇸
Monroeville, Pennsylvania, United States
Med Atlantic, Inc (Virginia Urology)
🇺🇸
Richmond, Virginia, United States
Southern Interior Medical Research Inc.
🇨🇦
Kelowna, British Columbia, Canada
Burlington Urology
🇨🇦
Burlington, Ontario, Canada
McGill Urology Associates
🇨🇦
Montreal, Quebec, Canada
Male/Female Health and Research Centre
🇨🇦
Barrie, Ontario, Canada
Centre for Advanced Urological Research
🇨🇦
Kingston, Ontario, Canada
London Health Sciences Centre
🇨🇦
London, Ontario, Canada
Urology Assoc./Urologic Medical Research
🇨🇦
Kitchener, Ontario, Canada
Urotec
🇨🇦
Oshawa, Ontario, Canada
The Health Institute for Men
🇨🇦
Toronto, Ontario, Canada
Univ. Health Network, Princess Margaret Hospital Prostate Centre
🇨🇦
Toronto, Ontario, Canada
Urology Research Options
🇺🇸
Aurora, Colorado, United States
Urology Enterprises
🇺🇸
Marietta, Georgia, United States
North Fulton Urology
🇺🇸
Roswell, Georgia, United States
St. Joseph's, Candler Health System
🇺🇸
Savannah, Georgia, United States
Urology of Indiana, LLC
🇺🇸
Indianapolis, Indiana, United States
Metropolitan Urology, PSC
🇺🇸
Jeffersonville, Indiana, United States
Wake Urology Associates
🇺🇸
Raleigh, North Carolina, United States
Michigan Medical, PC Urology
🇺🇸
Grand Rapids, Michigan, United States
Columbus Urology, Inc.
🇺🇸
Columbus, Ohio, United States
Urology Services Madigan Army Medical Center
🇺🇸
Tacoma, Washington, United States
Mich. Inst. of Urology
🇺🇸
Saint Clair Shores, Michigan, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Research Across America
🇺🇸
Dallas, Texas, United States
Summa Health System, Cancer Research Office
🇺🇸
Akron, Ohio, United States
Deaconess Medical Center
🇺🇸
Spokane, Washington, United States
Urology of Northern Ohio
🇺🇸
Elyria, Ohio, United States
State College Urologic Associates, Inc.
🇺🇸
State College, Pennsylvania, United States
Specialty Care Research
🇺🇸
Peoria, Illinois, United States
Medical Affiliated Research Ctr.
🇺🇸
Huntsville, Alabama, United States
Coastal Clinical Research
🇺🇸
Mobile, Alabama, United States
San Bernardino Urological Associates Medical Group
🇺🇸
San Bernardino, California, United States
Western Clinical Research, Inc.
🇺🇸
Torrance, California, United States
Atlantic Urological Associates
🇺🇸
Daytona Beach, Florida, United States
Advanced Research Institute
🇺🇸
New Port Richey, Florida, United States
Winter Park Urology Associates
🇺🇸
Orlando, Florida, United States
Panama City Urological Center
🇺🇸
Panama City, Florida, United States
Demaur Clinical Research Center
🇺🇸
Pembroke Pines, Florida, United States
Mid Atlantic Clinical Research
🇺🇸
Rockville, Maryland, United States
Anne Arundel Urology
🇺🇸
Annapolis, Maryland, United States
Urologic Surgeons, Ltd.
🇺🇸
Reno, Nevada, United States
The Urological Institute of Northeastern Research Department
🇺🇸
Albany, New York, United States
Lake Success Urological Associates
🇺🇸
Lake Success, New York, United States
NYU Urology Associates
🇺🇸
New York, New York, United States
University Urology Associates
🇺🇸
New York, New York, United States
Asheboro Urology Clinic
🇺🇸
Asheboro, North Carolina, United States
McKay Urology
🇺🇸
Charlotte, North Carolina, United States
Parkhurst Research Organization
🇺🇸
Bethany, Oklahoma, United States
Urologic Specialists of Oklahoma Research Department
🇺🇸
Tulsa, Oklahoma, United States
University Urological Research Institute
🇺🇸
Providence, Rhode Island, United States
University of Pittsburgh, Department of Urology
🇺🇸
Pittsburgh, Pennsylvania, United States
Columbia Urological Associates
🇺🇸
Columbia, South Carolina, United States
Carolina Urologic Research Center
🇺🇸
Myrtle Beach, South Carolina, United States
Professional Quality Research
🇺🇸
Austin, Texas, United States
University of Tennessee, Dept. of Urology
🇺🇸
Memphis, Tennessee, United States
Devine-Tidewater Urology
🇺🇸
Norfolk, Virginia, United States
Urology San Antonio Research, PA
🇺🇸
San Antonio, Texas, United States
Sanatorio Municipal
🇦🇷
Buenos Aires, Argentina
Mor Urology
🇨🇦
Newmarket, Ontario, Canada
The Fe/Male Health Centres
🇨🇦
Oakville, Ontario, Canada
Les Urologues Associes du CHUM
🇨🇦
Montreal, Quebec, Canada
Roger Buckley, MD
🇨🇦
Willowdale, Ontario, Canada
Urology South Shore Research
🇨🇦
Greenfield Park, Quebec, Canada
Southwest Florida Urologic Associates
🇺🇸
Fort Myers, Florida, United States
South Florida Medical Research
🇺🇸
Aventura, Florida, United States
Urology Associates, PC
🇺🇸
Manhasset, New York, United States
Alberta Urology Inst.. Research Center
🇨🇦
Edmonton, Alberta, Canada