Zoledronate, Calcium, and Vitamin D in Preventing Bone Loss in Women Receiving Adjuvant Chemotherapy for Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Zoledronate plus calcium and vitamin D may prevent bone loss in patients receiving adjuvant chemotherapy for breast cancer. It is not yet known which regimen is more effective in preventing bone loss. PURPOSE: This randomized phase III trial is comparing two regimens of zoledronate plus calcium and vitamin D to see how well they work in preventing bone loss in women who are receiving adjuvant chemotherapy for breast cancer.

Detailed Description
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OBJECTIVES: Compare the bone mineral density in the lumbar spine after 12 and 36 months of therapy with zoledronate, calcium, and cholecalciferol (vitamin D) in women with breast cancer receiving adjuvant chemotherapy. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to intent to treat with tamoxifen (yes vs no) and node status (negative vs positive vs unknown [for patients receiving neoadjuvant therapy]). Patients are randomized to 1 of 2 treatment arms. Arm I: Beginning on the first day of adjuvant chemotherapy (or within 3 months after the first day), patients receive zoledronate IV over at least 15 minutes once every 3 months during months 1-24 and oral calcium and oral cholecalciferol (vitamin D) daily during months 1-36. Arm II: Beginning on the first day of adjuvant chemotherapy (or within 3 months after the first day), patients receive oral calcium and oral vitamin D daily during months 1-36 and zoledronate IV over at least 15 minutes once every 3 months during months 13-36. PROJECTED ACCRUAL: Approximately 400 patients (200 per treatment arm) will be accrued for this study within 24 months.

Official Title
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Phase III Trial of Intravenous Zoledronic Acid (Zometa) in the Prevention of Bone Loss in Localized Breast Cancer Patients With Chemotherapy-Induced Ovarian Failure

Conditions
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Breast Cancer, Osteoporosis

Intervention / Treatment
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* Dietary Supplement: calcium salts
* Dietary Supplement: cholecalciferol
* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast by fine needle aspirate, biopsy (tru-cut, core, stereotactic), lumpectomy, or modified radical mastectomy Stage I-III (any T, any N, M0) Stage IV due solely to supraclavicular node involvement allowed Plan to use adjuvant chemotherapy* with or without adjuvant endocrine therapy* Subsequent adjuvant hormonal therapy with an aromatase inhibitor allowed in women rendered postmenopausal by adjuvant chemotherapy NOTE: *Must be specified prior to study entry Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 40 and over Sex: Female Menopausal status: See Disease Characteristics Premenopausal, defined as actively menstruating or last menstrual period occurred within 6 months prior to study entry Prior hysterectomy without bilateral oophorectomy and estradiol and follicle-stimulating hormone within premenopausal range prior to the initiation of chemotherapy allowed Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No more than 3 months since prior adjuvant chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: Not specified Surgery: See Disease Characteristics See Menopausal status Other: No other concurrent bisphosphonates No concurrent digoxin No concurrent tetracycline Concurrent neoadjuvant therapy allowed Concurrent enrollment on therapeutic adjuvant clinical trials allowed provided the therapeutic trial does not preclude participation in this trial

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Female

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic acid initial tx<br>Zoledronic acid + calcium + Vit D for 2 years, followed by Calcium + vit D for 1 year | Dietary Supplement: calcium salts<br>* 1000 mg PO per day<br>Dietary Supplement: cholecalciferol<br>* 400 IU PO per day<br>* Other names: Vitamin D;Drug: zoledronic acid<br>* 4 mg IV infusion q 3 months, months 1-24 in Zoledronic acid initial tx arm and months 13-36 in calcium + vit D initial tx arm<br>* Other names: Zometa;|
| Experimental: Calcium + Vit D initial Tx<br>Calcium + vitamin D for 1 year followed by zoledronic acid + calcium + vit D for 2 years | Dietary Supplement: calcium salts<br>* 1000 mg PO per day<br>Dietary Supplement: cholecalciferol<br>* 400 IU PO per day<br>* Other names: Vitamin D;Drug: zoledronic acid<br>* 4 mg IV infusion q 3 months, months 1-24 in Zoledronic acid initial tx arm and months 13-36 in calcium + vit D initial tx arm<br>* Other names: Zometa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density in the lumbar spine |  | 12 months from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density in the lumbar spine |  | 36 months post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, stage I breast cancer, stage II breast cancer, stage IV breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer