Clinical trial NCT00129142: Toremifene Citrate for Prevention of Bone Fractures in Men With Prostate Cancer on Androgen Deprivation Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Osteoporosis
Fractures
Keywords: Prostate cancer
Bone Loss
Osteoporosis
Fractures
Androgen Deprivation Therapy
Lead sponsor: GTx
Sponsor class: INDUSTRY
First posted: 2005-08-11
Enrollment: 1200
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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 outcomes:
measure: Percentage of subjects with at least one new or worsening vertebral fracture at 24 months
measure: Percentage of subjects with a clinical fragility fracture at 12 and 24 months
measure: Percent change from baseline in lumbar bone mineral density (BMD) as measured by dual energy x-ray absorptiometry (DEXA) scan at 24 months
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Urology Centers of Alabama
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Urology Medical Center Clinical Trials
state: California
city: Culver City
country: United States
facility: Urological Sciences Research Foudation
state: California
city: Fresno
country: United States
facility: Urological Associates of Central CA
state: California
city: La Mesa
country: United States
facility: Center of Urologic Research
state: California
city: Laguna Woods
country: United States
facility: South Orange County Medical Research Center
state: California
city: Palo Alto
country: United States
facility: Palo Alto VA
state: California
city: San Bernadino
country: United States
facility: San Bernadino Urological Associates
state: California
city: San Diego
country: United States
facility: Urological Physicians of San Diego
state: California
city: San Diego
country: United States
facility: Veterans Medical Research Foundation
state: California
city: Santa Monica
country: United States
facility: Pacific Clinical Research
state: California
city: Tarzana
country: United States
facility: West Coast Clinical Research
state: California
city: Torrance
country: United States
facility: Western Clinical Research, Inc.
state: California
city: Denver
country: United States
facility: Urology Associates
state: Colorado
city: Wheat Ridge
country: United States
facility: Western Urological Research
state: Colorado
city: New Haven
country: United States
facility: Urologic Center
state: Connecticut
city: Trumball
country: United States
facility: Urological Associates of Bridgeport
state: Connecticut
city: Waterbury
country: United States
facility: Connecticut Clinical Research
state: Connecticut
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Aventura
country: United States
facility: South Florida Medical Research
state: Florida
city: Clearwater
country: United States
facility: Urology Consultants Inc.
state: Florida
city: Daytona Beach
country: United States
facility: Atlantic Urological Associates
state: Florida
city: Inverness
country: United States
facility: Urosearch
state: Florida
city: Lakeland
country: United States
facility: Lakeland Regional Medical Center
state: Florida
city: New Port Richey
country: United States
facility: Advance Research Institute
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 Beach
country: United States
facility: Panama City Urology
state: Florida
city: St. Petersburg
country: United States
facility: Pinellas Urology
state: Florida
city: Tallahassee
country: United States
facility: Southeastern Research Group
state: Florida
city: Tampa
country: United States
facility: Tampa Bay Urology
state: Florida
city: Tavares
country: United States
facility: UroSearch
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic-Florida
state: Florida
city: Atlanta
country: United States
facility: Midtown Urology
state: Georgia
city: Atlanta
country: United States
facility: Georgia Urology
state: Georgia
city: Atlanta
country: United States
facility: St. Joseph Research Institute
state: Georgia
city: Augusta
country: United States
facility: Augusta VAMC
state: Georgia
city: Columbus
country: United States
facility: Southeastern Medical Research Institute
state: Georgia
city: Marietta
country: United States
facility: Urology Enterprises
state: Georgia
city: Rome
country: United States
facility: Harbin Clinic Department of Urology Research
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: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Chicago
country: United States
facility: Prairie Medical Associates
state: Illinois
city: Galesburg
country: United States
facility: Medical and Surgical Specialists
state: Illinois
city: Peoria
country: United States
facility: Special Care Research
state: Illinois
city: Greenwood
country: United States
facility: Urology of Indiana, LLC
state: Indiana
city: Greenwood
country: United States
facility: MMPC Urology
state: Indiana
city: Jeffersonville
country: United States
facility: Metropolitan Urology
state: Indiana
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: New Orleans
country: United States
facility: LSUHSC/Stanley Scott Cancer Center
state: Louisiana
city: Shreveport
country: United States
facility: Regional Urology LLC
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Urology P.A.
state: Maryland
city: Baltimore
country: United States
facility: Maryland Prostate Center: University of Maryland Medical Center
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: Worcester
country: United States
facility: The Fallon Clinic
state: Massachusetts
city: Worcester
country: United States
facility: Wayne Glazier
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont Medical
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Urology Department
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Urology
state: Minnesota
city: Kansas
country: United States
facility: Kansas City Urology, PC
state: Missouri
city: St Louis
country: United States
facility: PPS Clinical Research
state: Missouri
city: St. Louis
country: United States
facility: Urologic Research Center
state: Missouri
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: Hamilton
country: United States
facility: Hamilton Urology PA
state: New Jersey
city: Lawrenceville
country: United States
facility: Lawrenceville Urology Associates
state: New Jersey
city: Marlton
country: United States
facility: Assoc. Urologic Specialists
state: New Jersey
city: Willingboro
country: United States
facility: Urology Healthcare Associates
state: New Jersey
city: Albuquerque
country: United States
facility: Urology Group of New Mexico
state: New Mexico
city: Albany
country: United States
facility: Urology Inst. Of New York
state: New York
city: Albany
country: United States
facility: William Oberheim
state: New York
city: Elmont
country: United States
facility: Metropolitan Urologic Services, PC
state: New York
city: Garden City
country: United States
facility: Urological Surgeons of Long Island
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
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 , PC
state: New York
city: Syracuse
country: United States
facility: Associated Urologists of CNY
state: New York
city: Williamsville
country: United States
facility: Center for Urologic Research WNY, LLC
state: New York
city: Asheboro
country: United States
facility: Asheboro Urology
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Greensboro
country: United States
facility: The Urology Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Urology
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Bismarck
country: United States
facility: Odyssey Research
state: North Dakota
city: Akron
country: United States
facility: Summa Health Care
state: Ohio
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Lerner College of Medicine
state: Ohio
city: Columbus
country: United States
facility: Colombus Urology Research
state: Ohio
city: Elyria
country: United States
facility: Urology of Northern Ohio
state: Ohio
city: Parma
country: United States
facility: Southwest Urology
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Tulsa
country: United States
facility: Urologic Specialists of Oklahoma, Inc.
state: Oklahoma
city: Corvallis
country: United States
facility: The Corvallis Clinic
state: Oregon
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
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: Philadelphia
country: United States
facility: Ginsberg and Harkaway Urology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: State College
country: United States
facility: State College Urologic Association
state: Pennsylvania
city: Providence
country: United States
facility: University Urological Research Institute
state: Rhode Island
city: Greer
country: United States
facility: Radiant Research
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Memphis
country: United States
facility: Southeast Urology Network
state: Tennessee
city: Nashville
country: United States
facility: Ace Research Specialists
state: Tennessee
city: Nashville
country: United States
facility: Center for Urological Treatment
state: Tennessee
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Austin
country: United States
facility: Professional Quality Research
state: Texas
city: Houston
country: United States
facility: Breco Research
state: Texas
city: San Antonio
country: United States
facility: Urology Consultants, PA
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research, PA
state: Texas
city: Temple
country: United States
facility: Scott and White Clinical Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake City Research
state: Utah
city: Alexandria
country: United States
facility: Adult and Pediatric Urologists of Northern VA
state: Virginia
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: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Seattle
country: United States
facility: Seattle VAMC
state: Washington
city: Spokane
country: United States
facility: Deaconess Medical Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Medical School: Clinical Trials
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Michael's Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital Department of Urology
state: Wisconsin
city: Cheyenne
country: United States
facility: Wyoming Research Foundation
state: Wyoming
city: Mexico City
country: Mexico
facility: American British Cowdray Hospital
state: D. F
city: Mexico City
country: Mexico
facility: Centro Medico Dalinde
state: D. F
city: Mexico City
country: Mexico
facility: Hospital General de Mexico
state: D. F
city: Mexico City
country: Mexico
facility: Hospital Regional "Gabriel Mancera", IMSS
state: D.f,
city: Mexico City
country: Mexico
facility: Centro Medico Naval
state: D.f.
city: Mexico City
country: Mexico
facility: Hospital General de Zona No. 1-A
state: D.f.
city: Mexico City
country: Mexico
facility: Clinica Londres
state: D.f.
city: Mexico City
country: Mexico
facility: Hospital Central Militar, SDN
state: D.f.
city: Mexico City
country: Mexico
facility: Hospital Medica Sur
state: D.f.
city: Mexico City
country: Mexico
facility: Hospital de Oncologia CMN Siglo XXI, IMSS
state: D.f.
city: Mexico City
country: Mexico
facility: Hospital General de Zona No. 26, Mexico D.F.
state: D.f.
city: Mexico City
country: Mexico
facility: Hospital General Region 1 de Octubre, ISSSTE
state: D.F
city: Guadalajara
country: Mexico
facility: Hospital Civil Viejo "Fray Antonio Alcalde"
state: Jal
city: Guadalajara
country: Mexico
facility: Centro Medico de Occidente-IMSS
state: Jal
city: Guadalajara
country: Mexico
facility: Hospital Regional Dr Valentin Gomez Farias, ISSSTE
state: Jal
city: Monterrey
country: Mexico
facility: Hospital Regional de Especialidades
state: N.l.
city: Monterrey
country: Mexico
facility: Hospital Universitario
state: N.l.
city: San Luis Potosi
country: Mexico
facility: Hospital Ignacio Morones Prieto
state: S.l.p.
city: San Luis Potosi
country: Mexico
facility: Hospital General de Zona con UMF No. 2 San Luis Potosi
state: S.l.p.
Study officials:
affiliation: GTx
name: Mitchell Steiner, M.D.
role: STUDY_DIRECTOR
References:
citation: Smith MR, Morton RA, Barnette KG, Sieber PR, Malkowicz SB, Rodriguez D, Hancock ML, Steiner MS. Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2013 Jan;189(1 Suppl):S45-50. doi: 10.1016/j.juro.2012.11.016.
citation: Morgans AK, Hancock ML, Barnette KG, Steiner MS, Morton RA, Smith MR. Racial differences in bone mineral density and fractures in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2012 Mar;187(3):889-93. doi: 10.1016/j.juro.2011.10.136. Epub 2012 Jan 15.