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

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)

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).

Study Overview

• Status: Completed
• Conditions: Preneoplastic Conditions; Prostatic Intraepithelial Neoplasia
• Intervention / Treatment: Drug: Toremifene 20 mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 1589
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Italiano de Buenos Aires
  • Buenos Aires, Argentina
    • Hospital Pirovano
  • Buenos Aires, Argentina
    • Sanatorio Municipal
  • Buenos Aires, Argentina
    • Centro Urologico Buenos Aires
  • Buenos Aires, Argentina
    • Policlinico Bancario de Buenos Aires
  • Buenos Aires, Argentina
    • Servicio de Urologia
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Prostate Cancer Inst.
    • Edmonton, Alberta, Canada, T5H4B9
      • Alberta Urology Inst.. Research Center
  • British Columbia
    • Kelowna, British Columbia, Canada, V1H 2H4
      • Southern Interior Medical Research Inc.
    • Victoria, British Columbia, Canada, V8V3N1
      • Dr. G. Steinhoff Clinical Research
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B5B8
      • Allan B. Patrick, M.D. Professional corporation
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth Health Sciences Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Male/Female Health and Research Centre
    • Burlington, Ontario, Canada, L7N 3V2
      • Burlington Urology
    • Kingston, Ontario, Canada, K7L 3J7
      • Centre for Advanced Urological Research
    • Kitchener, Ontario, Canada, N2N 2B9
      • Urology Assoc./Urologic Medical Research
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Newmarket, Ontario, Canada, L3X 1W1
      • Mor Urology
    • Oakville, Ontario, Canada, L6H 3P1
      • The Fe/Male Health Centres
    • Oshawa, Ontario, Canada, L1H 7K4
      • Urotec
    • Toronto, Ontario, Canada, M6A 3B5
      • The Male Health Centre
    • Toronto, Ontario, Canada, M1P 2T7
      • The Health Institute for Men
    • Toronto, Ontario, Canada, M3B 3S6
      • Stanley Flax Medical Professional Corp.
    • Toronto, Ontario, Canada, M5G 2M9
      • Univ. Health Network, Princess Margaret Hospital Prostate Centre
    • Willowdale, Ontario, Canada, M2K 2W1
      • Roger Buckley, MD
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H3
      • Urology South Shore Research
    • Montreal, Quebec, Canada, H2X 1N8
      • Les Urologues Associes du CHUM
    • Montreal, Quebec, Canada, H3S 1Z1
      • McGill Urology Associates
    • Pointe Claire, Quebec, Canada, H9R 4S3
      • Ultra-Med, Inc.
    • Trois-Rivieres, Quebec, Canada, G9A 3V7
      • G.R.U.M.
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Ctr.
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Hope Research Inst.
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Urology
  • California
    • San Bernardino, California, United States, 92404
      • San Bernardino Urological Associates Medical Group
    • Torrance, California, United States, 90505
      • Western Clinical Research, Inc.
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Urology Research Options
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
    • Denver, Colorado, United States, 80210
      • Urology Associates, P.C.
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Surgical Group
    • Trumbull, Connecticut, United States, 06611
      • Urological Associates of Bridgeport
    • Waterbury, Connecticut, United States, 06708
      • Connecticut Clinical Research
  • Florida
    • Aventura, Florida, United States, 33180
      • South Florida Medical Research
    • Daytona Beach, Florida, United States, 32114
      • Atlantic Urological Associates
    • Fort Myers, Florida, United States, 33907
      • Southwest Florida Urologic Associates
    • New Port Richey, Florida, United States, 34652
      • Advanced Research Institute
    • Ocala, Florida, United States, 34474
      • Florida Foundation for Healthcare Research
    • Ocala, Florida, United States, 34474
      • Central Florida Urology Group/ UroSearch
    • Ocala, Florida, United States, 34471
      • UroSearch
    • Orlando, Florida, United States, 32803
      • Winter Park Urology Associates
    • Panama City, Florida, United States, 32405
      • Panama City Urological Center
    • Pembroke Pines, Florida, United States, 33028
      • Demaur Clinical Research Center
    • Pinellas Park, Florida, United States, 33782
      • DMI Research
    • Pinellas Park, Florida, United States, 33782
      • Urology Consultants
    • Sarasota, Florida, United States, 34237
      • Florida Urology Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Midtown Urology
    • Atlanta, Georgia, United States, 30342
      • Georgia Urology
    • Marietta, Georgia, United States, 30060
      • Urology Enterprises
    • Roswell, Georgia, United States, 30076
      • North Fulton Urology
    • Savannah, Georgia, United States, 31405
      • St. Joseph's, Candler Health System
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Specialty Care Research
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Urology of Indiana, LLC
    • Jeffersonville, Indiana, United States, 47130
      • Metropolitan Urology, PSC
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas City Urology Care, P.C.
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology, LLC
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Urology
    • Baltimore, Maryland, United States, 21201
      • Maryland Prostate Center: University of Maryland Medical Center
    • Greenbelt, Maryland, United States, 20770
      • Drs. Werner, Murdock, & Francis PA, Urology Associates
    • Hagerstown, Maryland, United States, 21742
      • Urology Center, PA
    • Rockville, Maryland, United States, 28050
      • Mid Atlantic Clinical Research
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology Research Assoc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital, Division of Urological Surgery
    • Brighton, Massachusetts, United States, 02135
      • Boston Clinical Trials
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Michigan Medical, PC Urology
    • Saint Clair Shores, Michigan, United States, 48081
      • Mich. Inst. of Urology
  • Minnesota
    • Sartell, Minnesota, United States, 56377
      • Adult & Pediatric Urology
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Louis Urological Surgeons
    • Florissant, Missouri, United States, 63031
      • Metropolitan Urological Specialists
    • Independence, Missouri, United States, 64055
      • Midwest Urology Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University Urologic Research Ctr.
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Urology PC
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Sheldon Freeman
    • Reno, Nevada, United States, 89502
      • Urologic Surgeons, Ltd.
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Coastal Urology Associates
    • Edison, New Jersey, United States, 08837
      • Central Jersey Clinical Research
    • Hamilton, New Jersey, United States, 08690
      • Hamilton Urology PA
    • Marlton, New Jersey, United States, 08053
      • Delaware Valley Urology
    • Mount Laurel, New Jersey, United States, 08054
      • Delaware Valley Urology
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Urology Group of New Mexico
  • New York
    • Albany, New York, United States, 12208
      • The Urological Institute of Northeastern Research Department
    • Elmont, New York, United States, 11003
      • Metropolitan Urologic Services, P.C.
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • Garden City, New York, United States, 11530
      • Urological Surgeons of Long Island
    • Lake Success, New York, United States, 11042
      • Lake Success Urological Associates
    • Manhasset, New York, United States, 11030
      • Urology Associates, PC
    • New York, New York, United States, 10016
      • University Urology Associates
    • New York, New York, United States, 10016
      • NYU Urology Associates
    • Oneida, New York, United States, 13421
      • CNY Urology
    • Staten Island, New York, United States, 10304
      • Staten Island Urological Research
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Asheboro Urology Clinic
    • Charlotte, North Carolina, United States, 28204
      • McKay Urology
    • Raleigh, North Carolina, United States, 27607
      • Wake Urology Associates
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Health System, Cancer Research Office
    • Cincinnati, Ohio, United States, 45212
      • Tri-State Urologic Services/PSC, Inc. d/b/a The Urology Group
    • Columbus, Ohio, United States, 43214
      • Columbus Urology, Inc.
    • Columbus, Ohio, United States, 43214
      • Capital Urology
    • Elyria, Ohio, United States, 44035
      • Urology of Northern Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Southwest Urology
  • Oklahoma
    • Bethany, Oklahoma, United States, 73008
      • Parkhurst Research Organization
    • Tulsa, Oklahoma, United States, 74104
      • Urologic Specialists of Oklahoma Research Department
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Oregon Urology Specialists
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Urologic Associates of Allentown
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Surgery, P.C.
    • Lancaster, Pennsylvania, United States, 17604
      • Urological Associates of Lancaster, Ltd.
    • Monroeville, Pennsylvania, United States, 15146
      • The Urology Institute
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh, Department of Urology
    • Pittsburgh, Pennsylvania, United States, 15212
      • Triangle Urological Group
    • State College, Pennsylvania, United States, 16801
      • State College Urologic Associates, Inc.
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • University Urological Research Institute
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Columbia Urological Associates
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Urology Center of the South
    • Knoxville, Tennessee, United States, 37920
      • Volunteer Research Group
    • Memphis, Tennessee, United States, 38119
      • Southeast Urology Network
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee, Dept. of Urology
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Texas
    • Austin, Texas, United States, 78756
      • Professional Quality Research
    • Dallas, Texas, United States, 75234
      • Research Across America
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research, PA
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake Research
    • Salt Lake City, Utah, United States, 84102
      • Advanced Clinical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Devine-Tidewater Urology
    • Richmond, Virginia, United States, 23235
      • Med Atlantic, Inc (Virginia Urology)
  • Washington
    • Seattle, Washington, United States, 98104
      • Seattle Urological Associates
    • Spokane, Washington, United States, 99204
      • Deaconess Medical Center
    • Tacoma, Washington, United States, 98405
      • Urologic Northwest Surgeons
    • Tacoma, Washington, United States, 98431
      • Urology Services Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Occurrence of a Positive Cancer Biopsy	To measure the occurrence of a positive cancer biopsy	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effect of Toremifene on Lipid Levels	Measure lipid levels including total cholesterol, LDL, HDL and Triglycerides % change from baseline	Up to 36 months
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
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
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
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
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

Collaborators and Investigators

• Sponsor: GTx
• Investigators: Principal Investigator: Samir Taneja, MD, NYU Langone Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: March 29, 2005
• First Submitted That Met QC Criteria: March 29, 2005
• First Posted (Estimated): March 30, 2005

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: cancer; Chemoprophylaxis; chemoprevention; neoplasia; premalignant; precancerous; Intraepithelial Prostatic Neoplasia; Neoplasia, Prostatic Intraepithelial
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Precancerous Conditions; Prostatic Intraepithelial Neoplasia; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Toremifene
• Other Study ID Numbers: G300104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No