Chemotherapy and/or Hormone Therapy With or Without Zoledronate in Treating Women With Stage II or Stage III Breast Cancer
NCT ID: NCT00072020
Last Updated: 2013-08-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
INTERVENTIONAL
2003-08-31
Brief Summary
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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
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
TREATMENT
NONE
Interventions
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zoledronic acid
adjuvant therapy
neoadjuvant therapy
Eligibility Criteria
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Inclusion Criteria
* 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)
18 Years
FEMALE
No
Sponsors
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University of Sheffield
OTHER
Principal Investigators
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Robert E. Coleman, MD, FRCP
Role:
Cancer Research Centre at Weston Park Hospital
Victoria Hiley
Role:
University of Leeds
References
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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 RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, Gil M, Houston SJ, Grieve RJ, Barrett-Lee PJ, Ritchie D, Pugh J, Gaunt C, Rea U, Peterson J, Davies C, Hiley V, Gregory W, Bell R; AZURE Investigators. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011 Oct 13;365(15):1396-405. doi: 10.1056/NEJMoa1105195. Epub 2011 Sep 25.
Coleman R, Woodward E, Brown J, Cameron D, Bell R, Dodwell D, Keane M, Gil M, Davies C, Burkinshaw R, Houston SJ, Grieve RJ, Barrett-Lee PJ, Thorpe H. Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01-04) for women with stage II/III breast cancer. Breast Cancer Res Treat. 2011 Jun;127(2):429-38. doi: 10.1007/s10549-011-1429-y. Epub 2011 Mar 11.
Coleman RE, Winter MC, Cameron D, Bell R, Dodwell D, Keane MM, Gil M, Ritchie D, Passos-Coelho JL, Wheatley D, Burkinshaw R, Marshall SJ, Thorpe H; AZURE (BIG01/04) Investigators. The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer. Br J Cancer. 2010 Mar 30;102(7):1099-105. doi: 10.1038/sj.bjc.6605604. Epub 2010 Mar 16.
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.
Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.
Coleman R, Cameron D, Dodwell D, Bell R, Wilson C, Rathbone E, Keane M, Gil M, Burkinshaw R, Grieve R, Barrett-Lee P, Ritchie D, Liversedge V, Hinsley S, Marshall H; AZURE investigators. Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial. Lancet Oncol. 2014 Aug;15(9):997-1006. doi: 10.1016/S1470-2045(14)70302-X. Epub 2014 Jul 15.
Other Identifiers
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CDR0000335111
Identifier Type: REGISTRY
Identifier Source: secondary_id
EU-20315
Identifier Type: -
Identifier Source: secondary_id
ISRCTN79831382
Identifier Type: -
Identifier Source: secondary_id
BIG-1-04
Identifier Type: -
Identifier Source: secondary_id
SHEFF-AZURE
Identifier Type: -
Identifier Source: org_study_id