Zoledronate in Preventing Bone Loss in Premenopausal Women Receiving Chemotherapy After Surgery For Early Stage Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: It is not yet known whether zoledronate is effective in preventing bone loss in premenopausal women who are receiving adjuvant chemotherapy after undergoing surgery for early stage breast cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate in preventing bone loss in premenopausal women who are receiving chemotherapy after surgery for early stage breast cancer.

Detailed Description
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OBJECTIVES: Compare the changes in bone mineral density (BMD) and bone turnover that occur in premenopausal women with resected early stage breast cancer during and after 6 months of adjuvant chemotherapy. Determine the factors that predict bone loss during chemotherapy, particularly induction of amenorrhea, type of chemotherapeutic regimen, glucocorticoid exposure, and baseline BMD, in these patients. Determine whether zoledronate prevents bone loss in these patients when given during and after adjuvant chemotherapy. Determine the effect of zoledronate on markers of bone turnover in these patients during and after adjuvant chemotherapy. Determine whether the effect on markers of bone turnover predicts response to zoledronate in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to estrogen receptor status (positive vs negative), progesterone receptor status (positive vs negative), and adjuvant chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive zoledronate IV over 15 minutes on day 1. Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, treatment repeats every 3 months for up to 4 courses in the absence of disease progression. Patients also receive calcium and cholecalciferol (vitamin D) supplements daily. Quality of life is assessed at baseline and at 6 and 12 months. Patients are followed at 1 year. PROJECTED ACCRUAL: A total of 120 patients (60 per treatment arm) will be accrued for this study.

Official Title
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A Randomized, Placebo Controlled Trial Of Zoledronic Acid For The Prevention Of Bone Loss In Premenopausal Women With Early Stage Breast Cancer

Conditions
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Breast Cancer, Osteoporosis

Intervention / Treatment
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* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of localized breast cancer Stage I or II (T1-3, N0-2, M0) Planned adjuvant chemotherapy (after surgery) of at least 6 months in duration Hormone receptor status: Estrogen receptor and progesterone receptor status known PATIENT CHARACTERISTICS: Age 18 to 50 Sex Female Menopausal status Premenopausal or perimenopausal Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Creatinine less than 2 mg/dL Other No T score of less than 2.0 on bone mineral density (BMD) No fragility fracture No lumbar spine anatomy that would preclude accurate BMD measurement of a minimum of 3 lumbar vertebrae Not pregnant PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy No concurrent radiotherapy Surgery See Disease Characteristics Other At least 1 month since prior calcitonin At least 12 months since prior bisphosphonates given for more than 1 month duration No concurrent fluoride therapy (10 mg/day or more) No concurrent enrollment in another experimental drug study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: zoledronic acid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lumbar spine bone mineral density (BMD) at 6 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lumbar spine BMD at 12 and 24 months |  |  | 
| Total hip and femoral neck BMD at 6, 12, and 24 months |  |  | 
| Serum markers of bone turnover (osteocalcin, bone-specific alkaline phosphatase, and cross-linked C-telopeptide of type 1 collagen levels) measured every 6 weeks for 6 months, and at 9 and 12 months |  |  | 
| Quality of life as measured by the Short Form-36 instrument at baseline, and at 6 and 12 months |  |  | 
| Treatment costs |  |  | 

 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