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

Phase 3

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Other protocol-defined inclusion / exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
Upfront Zoledronic Acid	Zoledronic acid	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
Delayed Zoledronic Acid	Zoledronic acid	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
Upfront Zoledronic Acid	Letrozole	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
Delayed Zoledronic Acid	Letrozole	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

Primary Outcome Measures

Name	Time	Method
Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy	From Baseline - 12 months	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.

Secondary Outcome Measures

Name	Time	Method
Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years	From Baseline to Year 2, Year 3, Year 4, 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.
Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5	From Baseline to Year 1, Year 2, Year 3, Year 4, 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.
Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5	From baseline to Year 1, Year 2, Year 3, Year 4, 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.
Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3	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.