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

Prostatic Intraepithelial Neoplasia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00106691
• Other study ID #: G300104
• Status: Completed
• Phase: Phase 3
• Start date: January 2005
• Est. completion date: February 2010

Study information

• Verified date: May 2023
• Source: GTx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 1589
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma in Situ
• Neoplasms
• Precancerous Conditions
• Preneoplastic Conditions
• Prostatic Intraepithelial Neoplasia

Intervention

Drug:
• 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
The subject takes a placebo tablet identical in appearance to the toremifene 20mg tablet, administered by mouth daily for 360 days.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
GTx

Countries where clinical trial is conducted

United States,  Argentina,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Toremifene in the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia (PIN)	To measure the efficacy of toremifene citrate in men with high grade prostatic intraepithelial neoplasia (PIN). Prostate cancer-free survival distributions (Kaplan-Meier)	The outcome measurement time is up to 36 months
Primary	Occurrence of a Positive Cancer Biopsy	To measure the occurrence of a positive cancer biopsy	Up to 36 months
Secondary	The Effect of Toremifene on Lipid Levels	Measure lipid levels including total cholesterol, LDL, HDL and Triglycerides % change from baseline	Up to 36 months
Secondary	The Effect of Toremifene on Hormone Levels	% Change from baseline hormone levels, including total testosterone, free testosterone, dihydrotestosterone (DHT) and estradiol	Up to 36 months
Secondary	The Effect of Toremifene on Total PSA (Prostate Specific Antigen) Levels	To assess the effect of toremifene in the total PSA (prostate specific antigen) levels from baseline	Up to 36 months
Secondary	The Effect of Toremifene on the Mean Change at 36 Months in AUA (American Urological Association) Symptom Score	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	36 months
Secondary	Occurrence of High Grade PIN at the 12, 24, 36 Month Biopsies	To measure the occurrence of high grade PIN at the 12, 24, 36 Month intervals in the 360 days study.	Up to 36 months
Secondary	The Effect of Toremifene on % Free Serum PSA (Prostate Specific Antigen) Levels, Change From Baseline	To assess the effect of toremifene in % free serum PSA (prostate specific antigen) levels, change from baseline	36 months