Toremifene Citrate for Prevention of Bone Fractures in Men With Prostate Cancer on Androgen Deprivation Therapy

Prostate Cancer Clinical Trial

Official title:

A Randomized, Double Blind, Placebo Controlled, Multicenter Efficacy and Safety Study of Toremifene Citrate for Prevention of Bone Fractures in Men With Prostate Cancer on Androgen Deprivation Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129142
• Other study ID #: G300203
• Status: Completed
• Phase: Phase 3
• First received: August 9, 2005
• Last updated: November 13, 2013
• Start date: October 2003
• Est. completion date: November 2007

Study information

• Verified date: November 2013
• Source: GTx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Androgen deprivation therapy (ADT) treatment for prostate cancer decreases the natural hormone called testosterone. This type of therapy is very effective for the treatment of prostate cancer. However, one of the side effects is bone loss or thinning of the bones that can lead to osteoporosis and an increased risk of bone fractures (breaking of the bones). The purpose of the study is to determine whether or not the addition of toremifene citrate (the study drug) to therapy can prevent or decrease the number of bone fractures and to evaluate its impact on side effects associated with testosterone reduction therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

To be eligible for participation in this study, subjects must meet all of the following criteria (minor deviations may be discussed with the medical monitor for possible inclusions):

• Give voluntary, signed informed consent in accordance with institutional policies

• Be male, aged = 50 years

• Have histologically documented prostate cancer. Subjects with metastatic prostate cancer may still be considered for the study as long as they are not disqualified by other inclusion/exclusion criteria and there is a reasonable expectation that their medical condition will not interfere with the objectives of the study and that adequate follow-up and compliance with the study protocol can be achieved for the full 24-month duration of the study.

• Have been on:

• ADT treatment (either luteinizing hormone-releasing agonist [LHRHa] or orchiectomy) for at least 6 months; Or

• Intermittent LHRHa for at least the preceding 12 months is acceptable, but subjects must be maintained on uninterrupted treatment for the duration of this study once they are randomized into the study.

• Be aged = 70 years or have BMD of lumbar spine or femoral neck at or below the specified thresholds for study entry:

• Hologic BMD (g/cm2): L1-L4 - 0.926; Femoral neck - 0.717

• Lunar BMD (g/cm2): L1-L4 - 1.050; Femoral neck - 0.840

• Serum prostate-specific antigen (PSA) = 4 ng/mL

• Have a Zubrod performance status = 1

• Subject weight < 300 lbs (weight limitation of DEXA equipment)

• Agree to complete a daily diary of medication intake and to provide tablet containers for accurate counts

• Agree to use an effective method of contraception, if the partner is of childbearing age, while on study

• 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:

Subjects with any of the following will not be eligible for enrollment:

• Taking bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH), Forteo® (teriparatide), calcitonin, or oral glucocorticoids within 45 days of randomization

• Have any disease or condition that would preclude an accurate evaluation of radiographs of the thoracic and lumbar spine (at least eight evaluable vertebrae in the range T4 to L4) [for example, severe scoliosis, or sequelae of orthopedic procedures or other surgery]

• Have > 4 vertebral fragility fractures

• Have any history of other carcinomas within the last 5 years (except nonmelanoma cutaneous malignancies and superficial bladder cancer with no evidence of recurrence which will not be excluded). NOTE: Patients with cancers other than nonmelanoma cutaneous malignancies and superficial bladder cancer with no evidence of tumor recurrence for at least 5 years after definitive treatment will not be excluded from this study.

• Have Paget's disease of bone

• 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 for the full 24-month duration of the study

• Received treatment with other investigational agents within 30 days prior to randomization

• Taking finasteride (e.g., Proscar®), dutasteride (e.g., Avodart®), Danocrine® (danazol) or testosterone-like supplements, such as dehydroepiandrosterone (DHEA) [subject is eligible if he stops these agents for a total washout of 45 days prior to randomization and agrees not to use these agents for the duration of the study]

• Taking herbal medicine or dietary supplements for prostate health, such as PC SPES and saw palmetto (also known as Serenoa repens) [subject is eligible if he stops these agents for a total washout of 45 days prior to randomization and agrees not to use these agents for the duration of the study]. Lycopene and selenium are not prohibited and no washout is required.

• Have a history of thromboembolic disease including deep vein thrombosis or pulmonary embolus

• Have a history of chronic hepatitis or cirrhosis

• Have received prior treatment with toremifene

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Fractures
• Fractures, Bone
• Osteoporosis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Toremifene Citrate

Locations

Country	Name	City	State
Mexico	Centro Medico de Occidente-IMSS	Guadalajara	Jal
Mexico	Hospital Civil Viejo "Fray Antonio Alcalde"	Guadalajara	Jal
Mexico	Hospital Regional Dr Valentin Gomez Farias, ISSSTE	Guadalajara	Jal
Mexico	American British Cowdray Hospital	Mexico City	D. F
Mexico	Centro Medico Dalinde	Mexico City	D. F
Mexico	Centro Medico Naval	Mexico City	D.f.
Mexico	Clinica Londres	Mexico City	D.f.
Mexico	Hospital Central Militar, SDN	Mexico City	D.f.
Mexico	Hospital de Oncologia CMN Siglo XXI, IMSS	Mexico City	D.f.
Mexico	Hospital General de Mexico	Mexico City	D. F
Mexico	Hospital General de Zona No. 1-A	Mexico City	D.f.
Mexico	Hospital General de Zona No. 26, Mexico D.F.	Mexico City	D.f.
Mexico	Hospital General Region 1 de Octubre, ISSSTE	Mexico City	D.F
Mexico	Hospital Medica Sur	Mexico City	D.f.
Mexico	Hospital Regional "Gabriel Mancera", IMSS	Mexico City	D.f,
Mexico	Hospital Regional de Especialidades	Monterrey	N.l.
Mexico	Hospital Universitario	Monterrey	N.l.
Mexico	Hospital General de Zona con UMF No. 2 San Luis Potosi	San Luis Potosi	S.l.p.
Mexico	Hospital Ignacio Morones Prieto	San Luis Potosi	S.l.p.
United States	Summa Health Care	Akron	Ohio
United States	Urology Inst. Of New York	Albany	New York
United States	William Oberheim	Albany	New York
United States	Urology Group of New Mexico	Albuquerque	New Mexico
United States	Adult and Pediatric Urologists of Northern VA	Alexandria	Virginia
United States	Urologic Associates of Allentown	Allentown	Pennsylvania
United States	Advanced Urology Medical Center Clinical Trials	Anaheim	California
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Urology P.A.	Annapolis	Maryland
United States	Asheboro Urology	Asheboro	North Carolina
United States	Georgia Urology	Atlanta	Georgia
United States	Midtown Urology	Atlanta	Georgia
United States	St. Joseph Research Institute	Atlanta	Georgia
United States	Augusta VAMC	Augusta	Georgia
United States	Professional Quality Research	Austin	Texas
United States	South Florida Medical Research	Aventura	Florida
United States	Urologic Surgery	Bala Cynwyd	Pennsylvania
United States	Maryland Prostate Center: University of Maryland Medical Center	Baltimore	Maryland
United States	Odyssey Research	Bismarck	North Dakota
United States	Coastal Urology Associates	Brick	New Jersey
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Wyoming Research Foundation	Cheyenne	Wyoming
United States	Prairie Medical Associates	Chicago	Illinois
United States	The Urology Group	Cincinnati	Ohio
United States	Urology Consultants Inc.	Clearwater	Florida
United States	Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio
United States	North Idaho Urology	Coeur d'Alene	Idaho
United States	Colombus Urology Research	Columbus	Ohio
United States	Southeastern Medical Research Institute	Columbus	Georgia
United States	The Corvallis Clinic	Corvallis	Oregon
United States	Urological Sciences Research Foudation	Culver City	California
United States	Atlantic Urological Associates	Daytona Beach	Florida
United States	Urology Associates	Denver	Colorado
United States	Metropolitan Urologic Services, PC	Elmont	New York
United States	Urology of Northern Ohio	Elyria	Ohio
United States	Urological Associates of Central CA	Fresno	California
United States	Medical and Surgical Specialists	Galesburg	Illinois
United States	Urological Surgeons of Long Island	Garden City	New York
United States	The Urology Center	Greensboro	North Carolina
United States	MMPC Urology	Greenwood	Indiana
United States	Urology of Indiana, LLC	Greenwood	Indiana
United States	Radiant Research	Greer	South Carolina
United States	Urology Center, PA	Hagerstown	Maryland
United States	Hamilton Urology PA	Hamilton	New Jersey
United States	Urology Centers of Alabama	Homewood	Alabama
United States	Breco Research	Houston	Texas
United States	Urosearch	Inverness	Florida
United States	Metropolitan Urology	Jeffersonville	Indiana
United States	Kansas City Urology, PC	Kansas	Missouri
United States	Volunteer Research Group	Knoxville	Tennessee
United States	Center of Urologic Research	La Mesa	California
United States	South Orange County Medical Research Center	Laguna Woods	California
United States	Lakeland Regional Medical Center	Lakeland	Florida
United States	Urological Associates of Lancaster, Ltd.	Lancaster	Pennsylvania
United States	Sheldon Freeman	Las Vegas	Nevada
United States	Lawrenceville Urology Associates	Lawrenceville	New Jersey
United States	Arkansas Urology	Little Rock	Arkansas
United States	University of Wisconsin Medical School: Clinical Trials	Madison	Wisconsin
United States	Urology Enterprises	Marietta	Georgia
United States	Assoc. Urologic Specialists	Marlton	New Jersey
United States	Southeast Urology Network	Memphis	Tennessee
United States	Froedtert Memorial Lutheran Hospital Department of Urology	Milwaukee	Wisconsin
United States	St. Michael's Hospital	Milwaukee	Wisconsin
United States	Coastal Clinical Research	Mobile	Alabama
United States	The Urology Institute	Monroeville	Pennsylvania
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Ace Research Specialists	Nashville	Tennessee
United States	Center for Urological Treatment	Nashville	Tennessee
United States	Urology Associates	Nashville	Tennessee
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Urologic Center	New Haven	Connecticut
United States	LSUHSC/Stanley Scott Cancer Center	New Orleans	Louisiana
United States	Advance Research Institute	New Port Richey	Florida
United States	Mount Sinai School of Medicine	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	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	CNY Urology	Oneida	New York
United States	Winter Park Urology Associates	Orlando	Florida
United States	Palo Alto VA	Palo Alto	California
United States	Panama City Urology	Panama City Beach	Florida
United States	Southwest Urology	Parma	Ohio
United States	Special Care Research	Peoria	Illinois
United States	Ginsberg and Harkaway Urology	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University Urological Research Institute	Providence	Rhode Island
United States	Wake Urology	Raleigh	North Carolina
United States	Urologic Surgeons, Ltd.	Reno	Nevada
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Med Atlantic, Inc (Virginia Urology)	Richmond	Virginia
United States	Mayo Clinic Urology Department	Rochester	Minnesota
United States	Mid Atlantic Clinical Research	Rockville	Maryland
United States	Harbin Clinic Department of Urology Research	Rome	Georgia
United States	North Fulton Urology	Roswell	Georgia
United States	Beaumont Medical	Royal Oak	Michigan
United States	Salt Lake City Research	Salt Lake City	Utah
United States	Urology Consultants, PA	San Antonio	Texas
United States	Urology San Antonio Research, PA	San Antonio	Texas
United States	San Bernadino Urological Associates	San Bernadino	California
United States	Urological Physicians of San Diego	San Diego	California
United States	Veterans Medical Research Foundation	San Diego	California
United States	Pacific Clinical Research	Santa Monica	California
United States	St. Joseph's, Candler Health System	Savannah	Georgia
United States	Seattle VAMC	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	PPS Clinical Research	St Louis	Missouri
United States	Urologic Research Center	St. Louis	Missouri
United States	Park Nicollet Urology	St. Louis Park	Minnesota
United States	Pinellas Urology	St. Petersburg	Florida
United States	State College Urologic Association	State College	Pennsylvania
United States	Staten Island Urological Research , PC	Staten Island	New York
United States	Associated Urologists of CNY	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Southeastern Research Group	Tallahassee	Florida
United States	Tampa Bay Urology	Tampa	Florida
United States	West Coast Clinical Research	Tarzana	California
United States	UroSearch	Tavares	Florida
United States	Scott and White Clinical Hospital	Temple	Texas
United States	Western Clinical Research, Inc.	Torrance	California
United States	Urological Associates of Bridgeport	Trumball	Connecticut
United States	Urologic Specialists of Oklahoma, Inc.	Tulsa	Oklahoma
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Connecticut Clinical Research	Waterbury	Connecticut
United States	Cleveland Clinic-Florida	Weston	Florida
United States	Western Urological Research	Wheat Ridge	Colorado
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Center for Urologic Research WNY, LLC	Williamsville	New York
United States	Urology Healthcare Associates	Willingboro	New Jersey
United States	Piedmont Medical Research Associates	Winston-Salem	North Carolina
United States	The Fallon Clinic	Worcester	Massachusetts
United States	Wayne Glazier	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
GTx

Countries where clinical trial is conducted

United States,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects at 24 months with at least one new vertebral fracture determined by blinded central review of radiographs of the thoracic and lumbar spine
Secondary	Percentage of subjects with at least one new or worsening vertebral fracture at 24 months
Secondary	Percentage of subjects with a clinical fragility fracture at 12 and 24 months
Secondary	Percent change from baseline in lumbar bone mineral density (BMD) as measured by dual energy x-ray absorptiometry (DEXA) scan at 24 months