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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified January 2006 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: November 4, 2003
Last updated: August 1, 2013
Last verified: January 2006

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.

Condition Intervention Phase
Breast Cancer
Metastatic Cancer
Drug: zoledronic acid
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High Risk Localized Breast Cancer?

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival as assessed annually for 10 years

Secondary Outcome Measures:
  • 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

Study Start Date: August 2003
Detailed Description:



  • 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.


  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over


  • Female

Menopausal status

  • Premenopausal or postmenopausal

Performance status

  • Karnofsky 80-100% OR
  • ECOG 0-1

Life expectancy

  • Not specified


  • Not specified


  • Not specified


  • Creatinine ≤ 1.5 times upper limit of normal


  • 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



  • See Disease Characteristics

Endocrine therapy

  • See Disease Characteristics


  • See Disease Characteristics


  • 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


  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00072020

Sponsors and Collaborators
University of Sheffield
OverallOfficial: Robert E. Coleman, MD, FRCP Cancer Research Centre at Weston Park Hospital
OverallOfficial: Victoria Hiley University of Leeds
  More Information

Marshall H, Gregory W, Bell R, et al.: Adjuvant therapy with zoledronic acid (AZURE-BIG 01/04): The influence of menopausal status and age on treatment effects. [Abstract] J Clin Oncol 30 (Suppl 15): A-502, 2012.
Coleman R, Thorpe H, Cameron D, et al.: Zoledronic acid is well tolerated and can be safely administered with adjuvant chemotherapy first safety data from the AZURE trial (BIG01/04). [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2080, S107, 2006.

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00072020     History of Changes
Other Study ID Numbers: SHEFF-AZURE
CDR0000335111 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: November 4, 2003
Last Updated: August 1, 2013

Keywords provided by National Cancer Institute (NCI):
bone metastases
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs processed this record on May 23, 2017