The Use of Zoledronic Acid to Prevent Cancer-treatment Bone Loss in Post-menopausal Women Receiving Adjuvant Letrozole for Breast Cancer

Study Overview
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Brief Summary
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Post-menopausal breast cancer patients will receive letrozole 2.5 mg daily for the treatment of breast cancer and will be randomized to a treatment group to receive either upfront zoledronic acid 4 mg IV 15-minute infusion every 6 months or delayed start zoledronic acid 4 mg IV 15-minute infusion every 6 months. Delayed start zoledronic acid will be initiated when either the Bone Mineral Density T-score is below -2 Standard Deviations at either the lumbar spine or hip or any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the month 36 scheduled visit. Letrozole 2.5 mg will be given daily for 5 years.

Official Title
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The Use of Zoledronic Acid to Prevent Cancer-treatment Bone Loss in Post-menopausal Women Receiving Adjuvant Letrozole for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Zoledronic acid
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage I-IIIa breast cancer Postmenopausal Recent surgery for breast cancer Exclusion Criteria: Metastatic disease Invasive bilateral disease Clinical or radiological evidence of existing fracture in spine or hip Other protocol-defined inclusion / exclusion criteria may apply.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upfront Zoledronic Acid<br>Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months for 5 years beginning on Day 1. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1 | Drug: Zoledronic acid<br>* Zoledronic acid 4 mg Intravenous (IV)15 minute infusion every 6 months.<br>* Other names: Zometa®;Drug: Letrozole<br>* Letrozole tablets 2.5 mg/day/taken orally for 5 years.<br>* Other names: Femara®;|
| Experimental: Delayed Zoledronic Acid<br>Zoledronic acid 4 mg Intravenous (IV) 15 minute infusion every 6 months beginning when one of the following occurred: BMD T-score <= -2.0 SD at either the lumbar spine or total hip, any clinical fracture unrelated to trauma or an asymptomatic fracture discovered at the Month 36 visit. All participants took Letrozole tablets 2.5 mg/day for 5 years beginning on Day 1 | Drug: Zoledronic acid<br>* Zoledronic acid 4 mg Intravenous (IV)15 minute infusion every 6 months.<br>* Other names: Zometa®;Drug: Letrozole<br>* Letrozole tablets 2.5 mg/day/taken orally for 5 years.<br>* Other names: Femara®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100. | From Baseline - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100. | From Baseline to Year 2, Year 3, Year 4, Year 5 | 
| Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100. | From Baseline to Year 1, Year 2, Year 3, Year 4, Year 5 | 
| Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5 | Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100. | From baseline to Year 1, Year 2, Year 3, Year 4, Year 5 | 
| Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3 | Radiological Fracture at 36 months which was not present at baseline = (new fracture/number participant analyzed)*100. Evaluation of radiological fractures were based on central lab X-ray data. A subject with multiple fractures at the same time or multiple fractures with the same grade is counted only once for that treatment. | Year 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, letrozole, zoledronic acid, adjuvant, postmenopausal