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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Osteoporosis; Prostate Cancer

Treatments: Other: placebo; Drug: risedronate sodium; Dietary Supplement: calcium carbonate; Drug: Estrogen Antagonists; Dietary Supplement: cholecalciferol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00043069

CDR0000069502 (Registry Identifier)

NCCTG-N01C8

NCI-P02-0229

NCI-2012-02482 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 71 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

71 participants in 4 patient groups, including a placebo group

Arm I: calcium + cholecalciferol + placebo + estrogen

Active Comparator group

Description:

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.

Treatment:

Dietary Supplement: calcium carbonate

Drug: Estrogen Antagonists

Dietary Supplement: cholecalciferol

Other: placebo

Arm II: calcium + cholecalciferol + risedronate + estrogen

Experimental group

Description:

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.

Treatment:

Drug: risedronate sodium

Dietary Supplement: calcium carbonate

Drug: Estrogen Antagonists

Dietary Supplement: cholecalciferol

Arm III: calcium + cholecalciferol + placebo + estrogen

Placebo Comparator group

Description:

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.

Treatment:

Dietary Supplement: calcium carbonate

Drug: Estrogen Antagonists

Dietary Supplement: cholecalciferol

Other: placebo

Arm IV: calcium + cholecalciferol + risedronate + estrogen

Experimental group

Description:

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.

Treatment:

Drug: risedronate sodium

Dietary Supplement: calcium carbonate

Drug: Estrogen Antagonists

Dietary Supplement: cholecalciferol