A Study of Zoledronic Acid in the Prevention of Cancer Therapy-induced Bone Loss

Study Overview
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Brief Summary
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Breast cancer and osteoporosis are two of the most frequent diseases in women. Estrogen may be associated with bone loss and the risk of breast cancer because of its potent effects on the mitotic activity of breast epithelium and on bone turnover. This study is will assess the safety and efficacy of Zoledronic acid 4 mg, given every 3 months over 24 months, in improving bone mineral density in premenopausal women with hormone receptor negative breast cancer and adjuvant chemotherapeutic treatment compared to placebo. This study is not recruiting patients in the United States.

Official Title
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Influence of Zoledronic Acid on Bone Mineral Density and Bone Ultrasonometry in Premenopausal Women With Hormone Receptor Negative Breast Cancer and Adjuvant Chemotherapeutic Treatment

Conditions
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Primary Hormone Receptor Negative Breast Cancer in Premenopausal Women

Intervention / Treatment
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* Drug: Zoledronic Acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with histologically confirmed incident invasive breast cancer (T1-4) with no evidence of regional lymph node metastasis (N0) or distant metastasis (M0) and after complete primary tumor resection and axillary lymph node dissection less than 90 days before start of study drug treatment. Hormone receptor status is negative Patient is premenopausal (spontaneous and regular menses with premenopausal estradiol levels (>10ng/dL) Patient receives adjuvant standard chemotherapy with approved cytotoxic chemotherapeutic drugs (e.g. AC 4-6 cycles) (prior neoadjuvant CT is allowed) Bone density at study entry > -2.5 T-Score Exclusion Criteria: Prior treatment with bisphosphonates and estrogens or treatments for osteoporosis in addition to calcium and vitamin D Severe physical or psychological concomitant diseases and other known concurrent, severe medical disorder jeopardizing the life of the patient in the immediate future (e.g., myocardial infarction in previous six months, angina pectoris despite treatment, uncontrolled severe arterial hypertension, progressive cardiac or respiratory failure) Known hypersensitivity to bisphosphonates Abnormal renal function Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures and recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic Acid<br>Patients randomized into the Zometa arm received a total of 8 study drug infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months. | Drug: Zoledronic Acid<br>* 4 mg zoledronic acid in 5 mL concentrate solution. Plastic vials.<br>|
| Placebo Comparator: Placebo<br>Patients randomized into the Placebo Arm received a total of 8 placebo infusions which were applied every 3 months. Patients received treatment for 24 months every 3 months. | Drug: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Mineral Density (BMD) Measured by DXA at Lumbar Spine (L2-L4) Between Baseline and 24 Months. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density (BMD) Measured by QUS at os Calcis and Phalanges After 24 Months |  | 2 years | 
| Course of Biochemical Markers of Bone Turn Over (FSH, Estradiol (E2), Osteocalcin, PINP, Procollagene-I-peptid, Deoxypyridinoline in Serum) |  | 2 years | 
| Pathologic Fractures During 24 Month |  | 2 years | 
| Development of Metastases as Assessed by X-ray, CT, or MRI During 24 Months and During 60 Months |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, premenopausal, Bone Mineral density, Cancer therapy induced bone loss, zoledronic acid