Zoledronic Acid in the Prevention of Cancer Treatment Related Bone Loss in Postmenopausal Women Receiving 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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An Open-Label, Randomized, MultiCenter Study to Evaluate the Use of Zolendronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women With Estrogen Positive and/or Progesterone Positive Breast Cancer Receiving Letrozole as Adjuvant Therapy

Conditions
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Bone Loss, 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 or recently postmenopausal Recent surgery for breast cancer Estrogen Receptor positive and/or progesterone receptor positive hormone receptor status No prior treatment with letrozole Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Metastatic disease Invasive bilateral disease Clinical or radiological evidence of existing fracture in spine or hip Prior treatment with IV bisphosphonates in the past 12 months Current treatment with oral bisphosphonates ( must be discontinued within 3 weeks of baseline evaluation) Use of Tibolone within 6 months Prior use of parathyroid hormone for more than 1 week Previous or concomitant malignancy Abnormal renal function History of disease effecting bone metabolism Other protocol-defined exclusion criteria may apply.
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>Zolendronic 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>* Zolendronic 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>Zolendronic 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>* Zolendronic 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 |
| --- | --- | --- |
| Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy. | Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA). | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy. | Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA) | Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years. | 
| Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy. | Bone Mineral Density (g/cm^2) of the Lumbar Spine (L1-L4)as measured by dual energy x-ray absorptiometry (DXA) | Baseline, 5 years. | 
| Percentage Change in Bone Mineral Density (BMD) of the Total Hip at 12 Months, 2 Years, 3 Years, 4 Years and 5 Years After Therapy. | Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA) | Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years. | 
| Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline | At 3 years of therapy the percentage of participants with fractures as detected by X-ray and/ or bone scan. | Baseline,3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Loss, Osteopenia, Breast cancer, letrozole, zoledronic acid, postmenopausal