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 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