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

Inclusion Criteria: To be eligible for participation in this study, subjects must meet all of the followingcriteria (minor deviations may be discussed with the medical monitor for possibleinclusions):

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

• Be male, aged ≥ 50 years

• Have histologically documented prostate cancer. Subjects with metastatic prostatecancer may still be considered for the study as long as they are not disqualified byother inclusion/exclusion criteria and there is a reasonable expectation that theirmedical condition will not interfere with the objectives of the study and thatadequate 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] ororchiectomy) for at least 6 months; Or

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

• Be aged ≥ 70 years or have BMD of lumbar spine or femoral neck at or below thespecified 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 containersfor accurate counts

• Agree to use an effective method of contraception, if the partner is of childbearingage, 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), parathyroidhormone (PTH), Forteo® (teriparatide), calcitonin, or oral glucocorticoids within 45days of randomization

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

• Have > 4 vertebral fragility fractures

• Have any history of other carcinomas within the last 5 years (except nonmelanomacutaneous malignancies and superficial bladder cancer with no evidence of recurrencewhich will not be excluded). NOTE: Patients with cancers other than nonmelanomacutaneous malignancies and superficial bladder cancer with no evidence of tumorrecurrence for at least 5 years after definitive treatment will not be excluded fromthis 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 illnessor psychological, familial, sociological, geographical or other concomitant conditionthat would not permit adequate follow-up and compliance with the study protocol forthe full 24-month duration of the study

• Received treatment with other investigational agents within 30 days prior torandomization

• 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 torandomization 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 andsaw palmetto (also known as Serenoa repens) [subject is eligible if he stops theseagents for a total washout of 45 days prior to randomization and agrees not to usethese agents for the duration of the study]. Lycopene and selenium are not prohibitedand no washout is required.

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

• Have a history of chronic hepatitis or cirrhosis

• Have received prior treatment with toremifene