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Zoledronate in Preventing Bone Loss in Postmenopausal Women Who Are Receiving Letrozole for Stage I, Stage II, or Stage IIIA Breast Cancer

Phase 3
Completed
Conditions
Breast Cancer
Osteoporosis
Interventions
Registration Number
NCT00107263
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Zoledronate may prevent bone loss in patients who are receiving letrozole. It is not yet known which schedule of zoledronate is more effective in preventing bone loss in patients with breast cancer.

PURPOSE: This randomized phase III trial is studying two different schedules of zoledronate to compare how well they work in preventing bone loss in postmenopausal women who are receiving letrozole for stage I, stage II, or stage IIIA breast cancer.

Detailed Description

OBJECTIVES:

* Compare the effectiveness of zoledronate vs standard care in reducing bone loss during the first 12 months of study treatment in postmenopausal women with stage I-IIIA breast cancer initiating letrozole after prior treatment with tamoxifen.

* Compare the effect of immediate vs delayed zoledronate, annually at 2-5 years post-baseline, in reducing bone loss in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to duration of prior tamoxifen therapy (≤ 2 years vs \> 2 years); time since tamoxifen therapy was discontinued (\< 1 vs ≥ 1 year); prior adjuvant chemotherapy (yes vs no); and baseline total lumbar spine or femoral neck bone mineral density (BMD) T-score (\> -1 standard deviation \[SD\] vs between -1 to -2 SD). Patients are randomized to 1 of 2 treatment arms.

* Arm I (immediate therapy): Patients receive oral letrozole once daily. Patients also receive zoledronate IV over 15 minutes once every 6 months.

* Arm II (delayed therapy): Patients receive oral letrozole as in arm I. Patients with radiologic evidence of bone loss after 1 year of letrozole therapy receive zoledronate as in arm I.

In both arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 550 patients (275 per treatment arm) will be accrued for this study within 28 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
558
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I: letrozole + zoledronateletrozolePatients receive oral letrozole once daily. Patients also receive zoledronate IV over 15 minutes once every 6 months. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.
Arm I: letrozole + zoledronatezoledronic acidPatients receive oral letrozole once daily. Patients also receive zoledronate IV over 15 minutes once every 6 months. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.
Arm II: letrozole + zoledronateletrozolePatients receive oral letrozole once daily. Patients with radiologic evidence of bone loss after 1 year of letrozole therapy receive zoledronate as in arm I. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.
Arm II: letrozole + zoledronatezoledronic acidPatients receive oral letrozole once daily. Patients with radiologic evidence of bone loss after 1 year of letrozole therapy receive zoledronate as in arm I. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Average intra-patient change in total lumbar spine (L1-L4) bone mineral density (BMD) as measured by dual energy x-ray absorptiometry at baseline and 1 year after completion of study treatmentat 12 months
Secondary Outcome Measures
NameTimeMethod
BMD (lumbar spine) annually for 5 years after completion of study treatmentUp to 5 years
Incidence of osteoporosisUp to 5 years
Loss of bone densityUp to 5 years
Incidence of bone fracturesUp to 5 years
Time to disease progressionUp to 5 years
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