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

Sponsor

GTx (Industry)

Overall Status

Completed

CT.gov ID

NCT00129142

Collaborator

(none)

1,200

Enrollment

155

Locations

Duration (Months)

7.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Osteoporosis Fractures	Drug: Toremifene Citrate	Phase 3

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double

Primary Purpose:

Prevention

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 Start Date :

Oct 1, 2003

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Percentage of subjects with at least one new or worsening vertebral fracture at 24 months []
Percentage of subjects with a clinical fragility fracture at 12 and 24 months []
Percent change from baseline in lumbar bone mineral density (BMD) as measured by dual energy x-ray absorptiometry (DEXA) scan at 24 months []

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urology Centers of Alabama	Homewood	Alabama	United States	35209
2	Coastal Clinical Research	Mobile	Alabama	United States	36608
3	Arkansas Urology	Little Rock	Arkansas	United States	72211
4	Advanced Urology Medical Center Clinical Trials	Anaheim	California	United States	92801
5	Urological Sciences Research Foudation	Culver City	California	United States	90232
6	Urological Associates of Central CA	Fresno	California	United States	93720
7	Center of Urologic Research	La Mesa	California	United States	91942
8	South Orange County Medical Research Center	Laguna Woods	California	United States	92653
9	Palo Alto VA	Palo Alto	California	United States	94305
10	San Bernadino Urological Associates	San Bernadino	California	United States	92404
11	Urological Physicians of San Diego	San Diego	California	United States	92103
12	Veterans Medical Research Foundation	San Diego	California	United States	92161
13	Pacific Clinical Research	Santa Monica	California	United States	90404
14	West Coast Clinical Research	Tarzana	California	United States	91356
15	Western Clinical Research, Inc.	Torrance	California	United States	90505
16	Urology Associates	Denver	Colorado	United States	80210
17	Western Urological Research	Wheat Ridge	Colorado	United States	80033
18	Urologic Center	New Haven	Connecticut	United States	06511
19	Urological Associates of Bridgeport	Trumball	Connecticut	United States	06611
20	Connecticut Clinical Research	Waterbury	Connecticut	United States	06708
21	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307
22	South Florida Medical Research	Aventura	Florida	United States	33180
23	Urology Consultants Inc.	Clearwater	Florida	United States	33761
24	Atlantic Urological Associates	Daytona Beach	Florida	United States	32114
25	Urosearch	Inverness	Florida	United States	34452
26	Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
27	Advance Research Institute	New Port Richey	Florida	United States	34652
28	Central Florida Urology Group/ UroSearch	Ocala	Florida	United States	34474
29	Florida Foundation for Healthcare Research	Ocala	Florida	United States	34474
30	Winter Park Urology Associates	Orlando	Florida	United States	32803
31	Panama City Urology	Panama City Beach	Florida	United States	32405
32	Pinellas Urology	St. Petersburg	Florida	United States	33710
33	Southeastern Research Group	Tallahassee	Florida	United States	32308
34	Tampa Bay Urology	Tampa	Florida	United States	33607
35	UroSearch	Tavares	Florida	United States	32778
36	Cleveland Clinic-Florida	Weston	Florida	United States	33331
37	Midtown Urology	Atlanta	Georgia	United States	30308
38	Georgia Urology	Atlanta	Georgia	United States	30342
39	St. Joseph Research Institute	Atlanta	Georgia	United States	30342
40	Augusta VAMC	Augusta	Georgia	United States	30912
41	Southeastern Medical Research Institute	Columbus	Georgia	United States	31904
42	Urology Enterprises	Marietta	Georgia	United States	30060
43	Harbin Clinic Department of Urology Research	Rome	Georgia	United States	30165
44	North Fulton Urology	Roswell	Georgia	United States	30076
45	St. Joseph's, Candler Health System	Savannah	Georgia	United States	31405
46	North Idaho Urology	Coeur d'Alene	Idaho	United States	83814
47	Prairie Medical Associates	Chicago	Illinois	United States	60616
48	Medical and Surgical Specialists	Galesburg	Illinois	United States	61401
49	Special Care Research	Peoria	Illinois	United States	61614
50	Urology of Indiana, LLC	Greenwood	Indiana	United States	46143
51	MMPC Urology	Greenwood	Indiana	United States	49546
52	Metropolitan Urology	Jeffersonville	Indiana	United States	47130
53	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
54	LSUHSC/Stanley Scott Cancer Center	New Orleans	Louisiana	United States	70112
55	Regional Urology LLC	Shreveport	Louisiana	United States	71106
56	Anne Arundel Urology P.A.	Annapolis	Maryland	United States	21401
57	Maryland Prostate Center: University of Maryland Medical Center	Baltimore	Maryland	United States	21201
58	Urology Center, PA	Hagerstown	Maryland	United States	21742
59	Mid Atlantic Clinical Research	Rockville	Maryland	United States	28050
60	The Fallon Clinic	Worcester	Massachusetts	United States	01605
61	Wayne Glazier	Worcester	Massachusetts	United States	01605
62	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
63	Beaumont Medical	Royal Oak	Michigan	United States	48073
64	Mayo Clinic Urology Department	Rochester	Minnesota	United States	55905
65	Park Nicollet Urology	St. Louis Park	Minnesota	United States	55416
66	Kansas City Urology, PC	Kansas	Missouri	United States	64131
67	PPS Clinical Research	St Louis	Missouri	United States	63141
68	Urologic Research Center	St. Louis	Missouri	United States	63141
69	Sheldon Freeman	Las Vegas	Nevada	United States	89109
70	Urologic Surgeons, Ltd.	Reno	Nevada	United States	89502
71	Coastal Urology Associates	Brick	New Jersey	United States	08724
72	Hamilton Urology PA	Hamilton	New Jersey	United States	08690
73	Lawrenceville Urology Associates	Lawrenceville	New Jersey	United States	08648
74	Assoc. Urologic Specialists	Marlton	New Jersey	United States	08053
75	Urology Healthcare Associates	Willingboro	New Jersey	United States	08046
76	Urology Group of New Mexico	Albuquerque	New Mexico	United States	87109
77	Urology Inst. Of New York	Albany	New York	United States	12208
78	William Oberheim	Albany	New York	United States	12208
79	Metropolitan Urologic Services, PC	Elmont	New York	United States	11003
80	Urological Surgeons of Long Island	Garden City	New York	United States	11530
81	University Urology Associates	New York	New York	United States	10016
82	Mount Sinai School of Medicine	New York	New York	United States	10029
83	CNY Urology	Oneida	New York	United States	13421
84	Staten Island Urological Research , PC	Staten Island	New York	United States	10304
85	Associated Urologists of CNY	Syracuse	New York	United States	13210
86	Center for Urologic Research WNY, LLC	Williamsville	New York	United States	14221
87	Asheboro Urology	Asheboro	North Carolina	United States	27203
88	University of North Carolina	Chapel Hill	North Carolina	United States	27559
89	The Urology Center	Greensboro	North Carolina	United States	27403
90	Wake Urology	Raleigh	North Carolina	United States	27607
91	Piedmont Medical Research Associates	Winston-Salem	North Carolina	United States	27103
92	Odyssey Research	Bismarck	North Dakota	United States	58501
93	Summa Health Care	Akron	Ohio	United States	44304
94	The Urology Group	Cincinnati	Ohio	United States	45212
95	Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio	United States	44195
96	Colombus Urology Research	Columbus	Ohio	United States	43214
97	Urology of Northern Ohio	Elyria	Ohio	United States	44035
98	Southwest Urology	Parma	Ohio	United States	44129
99	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
100	Urologic Specialists of Oklahoma, Inc.	Tulsa	Oklahoma	United States	12208
101	The Corvallis Clinic	Corvallis	Oregon	United States	97330
102	Oregon Urology Specialists	Springfield	Oregon	United States	97477
103	Urologic Associates of Allentown	Allentown	Pennsylvania	United States	18103
104	Urologic Surgery	Bala Cynwyd	Pennsylvania	United States	19004
105	Urological Associates of Lancaster, Ltd.	Lancaster	Pennsylvania	United States	17604
106	The Urology Institute	Monroeville	Pennsylvania	United States	15146
107	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
108	Ginsberg and Harkaway Urology	Philadelphia	Pennsylvania	United States	19141
109	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15232
110	State College Urologic Association	State College	Pennsylvania	United States	16801
111	University Urological Research Institute	Providence	Rhode Island	United States	02904
112	Radiant Research	Greer	South Carolina	United States	29651
113	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
114	Volunteer Research Group	Knoxville	Tennessee	United States	37920
115	Southeast Urology Network	Memphis	Tennessee	United States	38119
116	Ace Research Specialists	Nashville	Tennessee	United States	37203
117	Center for Urological Treatment	Nashville	Tennessee	United States	37203
118	Urology Associates	Nashville	Tennessee	United States	37209
119	Vanderbilt Medical Center	Nashville	Tennessee	United States	37232
120	Professional Quality Research	Austin	Texas	United States	78756
121	Breco Research	Houston	Texas	United States	77024
122	Urology Consultants, PA	San Antonio	Texas	United States	78229
123	Urology San Antonio Research, PA	San Antonio	Texas	United States	78229
124	Scott and White Clinical Hospital	Temple	Texas	United States	76508
125	Salt Lake City Research	Salt Lake City	Utah	United States	84124
126	Adult and Pediatric Urologists of Northern VA	Alexandria	Virginia	United States	22304
127	Devine Tidewater Urology	Norfolk	Virginia	United States	23502
128	Med Atlantic, Inc (Virginia Urology)	Richmond	Virginia	United States	23235
129	McGuire VA Medical Center	Richmond	Virginia	United States	23249
130	Seattle VAMC	Seattle	Washington	United States	98108
131	Deaconess Medical Center	Spokane	Washington	United States	99204
132	Madigan Army Medical Center	Tacoma	Washington	United States	98431
133	University of Wisconsin Medical School: Clinical Trials	Madison	Wisconsin	United States	53715
134	St. Michael's Hospital	Milwaukee	Wisconsin	United States	53209
135	Froedtert Memorial Lutheran Hospital Department of Urology	Milwaukee	Wisconsin	United States	53226
136	Wyoming Research Foundation	Cheyenne	Wyoming	United States	82001
137	American British Cowdray Hospital	Mexico City	D. F	Mexico	01120
138	Centro Medico Dalinde	Mexico City	D. F	Mexico	06760
139	Hospital General de Mexico	Mexico City	D. F	Mexico	06760
140	Hospital Regional "Gabriel Mancera", IMSS	Mexico City	D.f,	Mexico
141	Centro Medico Naval	Mexico City	D.f.	Mexico	01090
142	Hospital General de Zona No. 1-A	Mexico City	D.f.	Mexico	03300
143	Clinica Londres	Mexico City	D.f.	Mexico	06760
144	Hospital Central Militar, SDN	Mexico City	D.f.	Mexico	11649
145	Hospital Medica Sur	Mexico City	D.f.	Mexico	14050
146	Hospital de Oncologia CMN Siglo XXI, IMSS	Mexico City	D.f.	Mexico
147	Hospital General de Zona No. 26, Mexico D.F.	Mexico City	D.f.	Mexico
148	Hospital General Region 1 de Octubre, ISSSTE	Mexico City	D.F	Mexico	07300
149	Hospital Civil Viejo "Fray Antonio Alcalde"	Guadalajara	Jal	Mexico	44280
150	Centro Medico de Occidente-IMSS	Guadalajara	Jal	Mexico	44340
151	Hospital Regional Dr Valentin Gomez Farias, ISSSTE	Guadalajara	Jal	Mexico
152	Hospital Regional de Especialidades	Monterrey	N.l.	Mexico	64320
153	Hospital Universitario	Monterrey	N.l.	Mexico	64460
154	Hospital Ignacio Morones Prieto	San Luis Potosi	S.l.p.	Mexico	78240
155	Hospital General de Zona con UMF No. 2 San Luis Potosi	San Luis Potosi	S.l.p.	Mexico	78270