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Chemotherapy and/or Hormone Therapy With or Without Zoledronate in Treating Women With Stage II or Stage III Breast Cancer

Phase 3
Conditions
Breast Cancer
Metastatic Cancer
Registration Number
NCT00072020
Lead Sponsor
University of Sheffield
Brief Summary

RATIONALE: Zoledronate may delay or prevent the formation of bone metastases. It is not yet known whether chemotherapy and/or hormone therapy are more effective with or without zoledronate in preventing cancer recurrence and bone metastases in women with breast cancer.

PURPOSE: This randomized phase III trial is studying giving chemotherapy and/or hormone therapy together with zoledronate to see how well they work compared to chemotherapy and/or hormone therapy alone in preventing cancer recurrence and bone metastases in women with stage II or stage III breast cancer.

Detailed Description

OBJECTIVES:

Primary

* Compare disease-free survival of women with stage II or III breast cancer at high risk of relapse treated with neoadjuvant or adjuvant chemotherapy and/or hormonal therapy with vs without zoledronate.

Secondary

* Compare time to bone metastases, as first recurrence, in patients treated with these regimens.

* Compare time to bone metastases, per se, in patients treated with these regimens.

* Compare time to distant metastases in patients treated with these regimens.

* Compare overall survival in patients treated with these regimens.

* Compare the reduction in skeletal-related events (fractures, spinal cord compression, radiotherapy to the bone, surgery to the bone, and hypercalcemia) before and after the development of bone metastases in patients treated with these regimens.

* Determine the safety and toxicity of zoledronate in patients treated with these regimens.

* Correlate prognostic factors, such as estrogen-receptor and progesterone-receptor status, TNM stage, tumor grade, HER2/neu status, and menopausal status with treatment outcome in patients treated with these regimens.

* Determine more specific prognostic indicators for the development of bone metastases and factors that are able to predict specific benefit from bisphosphonate treatment using proteomics, tissue micro-array, and other modern techniques in these patients.

OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy. Patients also receive concurrent zoledronate IV over 15 minutes every 3-4 weeks for 6 doses, every 3 months for 8 doses, and then every 6 months for 5 doses in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive neoadjuvant or adjuvant chemotherapy and/or hormonal therapy alone.

After completion of study treatment, patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 3,300 patients (1,650 per treatment arm) will be accrued for this study within 3 years.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Disease-free survival as assessed annually for 10 years
Secondary Outcome Measures
NameTimeMethod
Time to bone metastases as first recurrence assessed annually for 10 years
Time to bone metastases per se as assessed annually for 10 years
Time to distant metastases as assessed annually for 10 years
Overall survival as assessed by final analysis at 10 years
Skeletal-related events prior to development of bone metastases as assessed annually for 10 years
Skeletal-related events following development of bone metastases as assessed annually for 10 years
Safety and toxicity of zoledronic acid as assessed annually for 10 years
Evaluation of the influence of prognostic factors (e.g., estrogen receptor or progesterone receptor [ER/PR] status, TNM stage, tumor grade, HER2/neu, and menopausal status) on treatment outcome
Analysis of tumor-specific mutations, proteomics and gene expression changes in tumor cells
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