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

August 1, 2013 updated by: University of Sheffield

Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High Risk Localized Breast Cancer?

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of primary breast cancer, meeting 1 of the following staging criteria:

    • Stage II
    • Stage III
    • T stage ≥ T1

  • Receiving OR scheduled to receive chemotherapy and/or endocrine therapy

    • For patients receiving neoadjuvant therapy

      • Tumor > 5 cm (T3), features of locally advanced disease (T4), OR biopsy-proven lymph node involvement (N1)
      • Scheduled to proceed to definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy
      • No more than 30 days between initiation of neoadjuvant therapy and start of study drug

    • For patients receiving adjuvant therapy

      • Must have undergone complete primary tumor resection and treatment of axillary lymph nodes*
      • Must have lymph node involvement
      • No prior neoadjuvant therapy**
      • No more than 60 days since prior definitive surgery NOTE: *Patients whose treatment plan includes further primary tumor resection and/or treatment of the axillary lymph nodes (e.g., clearance or radiotherapy) with curative intent after completion of chemotherapy are eligible provided the treatment is completed within 9 months of study entry

NOTE: **Preoperative endocrine therapy with a duration of < 30 days is not considered prior neoadjuvant therapy

  • No evidence of recurrent or metastatic disease
  • No history of breast cancer, except ductal carcinoma in situ or lobular carcinoma in situ

  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Female

Menopausal status

  • Premenopausal or postmenopausal

Performance status

  • Karnofsky 80-100% OR
  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Creatinine ≤ 1.5 times upper limit of normal

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No active dental problems, including dental abscess or infection of the jaw bone (e.g., maxilla or mandible)
  • No prior or current diagnosis of osteonecrosis of the jaw
  • No other malignancy within the past 5 years (including prior contralateral breast cancer) except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix

  • No history of disease with influence on bone metabolism, including any of the following:

    • Paget's disease of the bone
    • Primary hyperparathyroidism
    • Osteoporosis requiring treatment or likely to require treatment within the next 6 months
  • No other severe physical or psychological disease that would preclude study compliance
  • No known hypersensitivity to bisphosphonates

PRIOR CONCURRENT THERAPY:

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • See Disease Characteristics

Surgery

  • See Disease Characteristics

  • More than 4 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants)

    • Dental fillings, teeth scaling and polishing, or minor gingival surgery within the past 4 weeks are allowed

Other

  • More than 1 year since prior bisphosphonates
  • More than 30 days since prior investigational drugs
  • No concurrent investigational drugs (i.e., not locally approved for any indication)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease-free survival as assessed annually for 10 years

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sheffield

Investigators

  • Robert E. Coleman, MD, FRCP, Cancer Research Centre at Weston Park Hospital
  • Victoria Hiley, University of Leeds

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2003

Study Registration Dates

First Submitted

November 4, 2003

First Submitted That Met QC Criteria

November 5, 2003

First Posted (Estimate)

November 6, 2003

Study Record Updates

Last Update Posted (Estimate)

August 2, 2013

Last Update Submitted That Met QC Criteria

August 1, 2013

Last Verified

January 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHEFF-AZURE
  • CDR0000335111 (Registry Identifier: PDQ (Physician Data Query))
  • EU-20315
  • ISRCTN79831382
  • BIG-1-04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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