Calcium With or Without Estrogen and/or Risedronate in Preventing Osteoporosis in Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Preventing bone loss in patients who are undergoing androgen ablation for prostate cancer may decrease the risk of fractures and may help patients live more comfortably. It is not yet known whether calcium is more effective with or without estrogen and/or risedronate in preventing osteoporosis. PURPOSE: Randomized phase III trial to compare the effectiveness of two forms of calcium with or without estrogen and/or risedronate in preventing osteoporosis in patients with prostate cancer who are receiving androgen ablation therapy.

Detailed Description
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OBJECTIVES: Compare the change in bone mineral density in patients with prostate cancer who are receiving androgen-ablation therapy treated with calcium and cholecalciferol with or without conjugated estrogens and with or without risedronate. Compare the toxicity of these regimens in these patients. Compare the changes in bone markers in patients treated with these regimens. Compare the quality of life of patients treated with these regimens. Compare hot flashes in patients treated with these regimens. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to duration of therapy with luteinizing hormone-releasing hormone agonists (no more than 30 days vs 31 to 150 days vs 151 to 365 days vs more than 365 days). Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo daily. Arm II: Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo daily. Arm III: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo daily. Arm IV: Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate daily. Treatment in all arms continues for 2 years. Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years. Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years. PROJECTED ACCRUAL: A total of 282 patients (70 per treatment arm) will be accrued for this study within 14 months.

Official Title
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Osteoporosis Prevention in Prostate Cancer Patients Receiving Androgen Ablation Therapy: A Phase III Randomized, Placebo-Controlled, Double-Blind Study

Conditions
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Osteoporosis, Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: calcium carbonate
* Dietary Supplement: cholecalciferol
* Drug: Estrogen Antagonists
* Drug: risedronate sodium
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: History of prostate cancer No evidence of metastatic bony disease* NOTE: *Elevated prostate-specific antigen (PSA) allowed Meets one of the following criteria: Currently on treatment with androgen-ablation therapy in the adjuvant setting Rising PSA without other evidence of recurrent disease with planned treatment for at least 6 months No known osteoporosis or prior osteoporotic fracture Osteoporosis defined as bone density at the hip or spine of more than 2.5 standard deviations below the mean for young men PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic SGOT or SGPT no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase normal OR no greater than 1.5 times ULN with a normal bone scan Renal Creatinine no greater than 1.5 times ULN No prior symptomatic hypercalcemia or hypocalcemia Cardiovascular No active heart disease No congestive heart failure under active treatment No myocardial infarction within the past 5 years No coronary artery disease (CAD) with recent myocardial infarction Patients with a remote history of CAD who are only on medical treatment (e.g., antilipid agents) are allowed No prior thrombosis (deep vein thrombosis, stroke, or pulmonary embolism) or other known hypercoagulable state other than cancer Other Fertile patients must use effective contraception Triglycerides no greater than 250 mg/dL (treatment allowed) Able to complete questionnaire(s) by self or with assistance Able to swallow pills No prior hyperlipidemia (e.g., prior familial hyperlipidemia or fasting triglyceride greater than 250 mg/dL within the past 6 months) No sarcoidosis No parathyroid dysfunction No intolerance to bisphosphonates PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No concurrent chemotherapy Endocrine therapy See Disease Characteristics No concurrent systemic steroids Radiotherapy No concurrent radiotherapy Surgery More than 3 months since prior and no concurrent dental extraction, root canal, or dental implantation Other No prior bisphosphonates More than 5 years since prior percutaneous transluminal coronary angioplasty

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I: calcium + cholecalciferol + placebo + estrogen<br>Patients receive oral calcium, oral cholecalciferol, oral risedronate placebo, and oral estrogen placebo daily. Treatment in all arms continues for 2 years. Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years. Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years. | Dietary Supplement: calcium carbonate<br> <br> Dietary Supplement: cholecalciferol<br> <br> Drug: Estrogen Antagonists<br> <br> Other: placebo<br> <br> |
| Experimental: Arm II: calcium + cholecalciferol + risedronate + estrogen<br>Patients receive oral calcium, oral cholecalciferol, oral risedronate, and oral estrogen placebo daily. Treatment in all arms continues for 2 years. Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years. Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years. | Dietary Supplement: calcium carbonate<br> <br> Dietary Supplement: cholecalciferol<br> <br> Drug: Estrogen Antagonists<br> <br> Drug: risedronate sodium<br> <br> |
| Placebo Comparator: Arm III: calcium + cholecalciferol + placebo + estrogen<br>Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate placebo daily. Treatment in all arms continues for 2 years. Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years. Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years. | Dietary Supplement: calcium carbonate<br> <br> Dietary Supplement: cholecalciferol<br> <br> Drug: Estrogen Antagonists<br> <br> Other: placebo<br> <br> |
| Experimental: Arm IV: calcium + cholecalciferol + risedronate + estrogen<br>Patients receive oral calcium, oral cholecalciferol, low-dose oral conjugated estrogens, and oral risedronate daily. Treatment in all arms continues for 2 years. Quality of life is assessed at baseline, monthly for 6 months, and then at 1 and 2 years. Bone mineral density is assessed at baseline, 6 months, and 1 and 2 years. | Dietary Supplement: calcium carbonate<br> <br> Dietary Supplement: cholecalciferol<br> <br> Drug: Estrogen Antagonists<br> <br> Drug: risedronate sodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density by test at 1 and 2 years |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity questionnaires every 6 months |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer