Contact information
Type
Scientific
Primary contact
Mrs Claire Davies
ORCID ID
Contact details
Senior Trial Manager
Clinical Trials Research Unit
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 (0)113 343 1498
c.l.davies@leeds.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00072020
Protocol/serial number
N/A
Study information
Scientific title
Acronym
AZURE
Study hypothesis
Adjuvant treatment with 4mg zoledronic acid plus chemotherapy and/or endocrine therapy is superior to chemotherapy and/or endocrine therapy alone in improving the disease-free and bone metastasis-free survival of women with breast cancer at high risk of relapse.
Ethics approval
West Midlands Research Ethics Committee (ref: 03/7/029)
Protocol Version 1.1, dated April 2003 - 19/05/2003;
Protocol Version 1.2, dated June 2003 - 31/07/2003;
Protocol Version 2, dated December 2003 - 08/01/2004;
Protocol Version 3, dated February 2004 - 24/02/2004;
Protocol Version 4, dated July 2005 - 23/07/2005;
Protocol Version 5, dated September 2007 - 08/10/2007;
Protocol Version 6, dated August 2008 - 24/09/2008;
Protocol Version 7, dated August 2010 - 26/08/2010
All other centres will seek ethics approval before recruitment of the first participant.
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Breast cancer
Intervention
Patients are randomised to receive either (neo)adjuvant chemotherapy and/or endocrine therapy alone, or (neo)adjuvant chemotherapy and/or hormonal therapy plus zoledronic acid.
The AZURE trial reached target recruitment and therefore closed to recruitment on 20th Jan 2006.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
To determine whether zoledronic acid with chemotherapy and/or endocrine therapy is superior to chemotherapy and/or endocrine therapy alone in improving disease-free survival
Secondary outcome measures
To determine whether zoledronic acid with chemotherapy and/or endocrine therapy is superior to chemotherapy and/or endocrine therapy alone in terms of:
1. Invasive disease-free survival (Added 05/05/2011)
2. Time to bone metastases as first recurrence
3. Time to bone metastases per se
4. Time to distant metastases
5. Overall survival
6. Reducing skeletal-related events* prior to development of bone metastases
7. Reducing skeletal-related events* following development of bone metastases
Additional secondary objectives are:
1. To assess the safety and toxicity of zoledronic acid in this clinical setting
2. To evaluate the influence of prognostic factors, such as estrogen receptor (ER)/progesterone receptor (PR) status, tumour, node, metastasis (TNM) stage, tumour grade, human epidermal growth factor receptor 2 (HER2/neu) (if available) and menopausal status on treatment outcome
3. To use proteomics, tissue micro-array and other modern techniques to identify more specific prognostic indicators for the development of bone metastases and factors that are able to predict specific benefit from bisphosphonate treatment (to be investigated via sub-studies)
* Defined as: fractures, spinal cord compression, radiation therapy to bone, surgery to bone and hypercalcaemia
Overall trial start date
01/09/2003
Overall trial end date
30/09/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients with stage II or III primary breast cancer
1. Female patients with Stage II/III primary breast cancer, with T stage ≥T1
2. Patients should be receiving/scheduled to receive chemotherapy and/or endocrine therapy
3. Patients receiving neo-adjuvant therapy
a. Must have tumour size of >5 cm (T3), features of locally advanced disease (T4) or biopsy-proven lymph node involvement
b. Should be scheduled to proceed to definitive surgery$ and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy
c. Time between commencement of neoadjuvant treatment and planned start date of study drug should be ≤30 days
4. Patients receiving adjuvant therapy
a. Must have undergone complete primary tumour resection and treatment of the axillary lymph nodes*, without any prior neoadjuvant therapy#
b. Must have evidence of lymph node involvement
c. Time between definitive surgery and planned start date of study drug should be ≤60 days
5. Performance status: Karnofsky Index ≥80% or Eastern Cooperative Oncology Group (ECOG) 0 and 1
6. Women of childbearing potential must be using a reliable and appropriate method of contraception
7. Age ≥18 years
8. Patient must have given written informed consent prior to any study-specific procedures
$Final definitive surgery is considered to include re-operation for inadequate margins or another bona fide oncological indication
*Patients whose treatment plan is to proceed to further primary tumour resection and/or treatment of the axillary lymph nodes (e.g. clearance or radiotherapy) with curative intent after completion of chemotherapy would be eligible but this must be completed within 9 months of randomisation
#Pre-operative endocrine therapy of less than 30 days would not be classed as prior neoadjuvant therapy
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Added 05/05/2011: target 3300 (3352 at time of registration), recruited 3360
Participant exclusion criteria
1. Metastatic or recurrent breast cancer or a history of breast cancer (aside from ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]) prior to the currently diagnosed case
2. History of prior cancers within the preceding 5 years (including previous contralateral breast cancer), aside from non-melanomatous skin cancer or carcinoma in situ of the uterine cervix treated with curative intent
3. History of diseases with influence on bone metabolism, such as Pagets disease of bone, primary hyperparathyroidism or osteoporosis requiring treatment at the time of study entry or considered likely to become necessary within the subsequent 6 months
4. Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol
5. Prior treatment with bisphosphonates within the past year
6. Serum creatinine >1.5 x Upper Limit of Normal
7. Known hypersensitivity to bisphosphonates
8. Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), or a current or prior diagnosis of osteonecrosis of the jaw (ONJ)
9. Recent (within 4 weeks of study entry) or planned dental or jaw surgery (e.g. extractions, implants). Recent dental fillings, teeth scaling and polishing or minor gingival surgery do not exclude the patient.
10. Pregnancy or breast-feeding
11. Use of other investigational drugs in the 30 days prior to study entry. (Patients may be receiving treatments within a clinical trial providing the treatment under test has a licensed indication within your country).
Recruitment start date
01/09/2003
Recruitment end date
30/09/2006
Locations
Countries of recruitment
Australia, Ireland, Portugal, Spain, Taiwan, Thailand, United Kingdom
Trial participating centre
Senior Trial Manager
Leeds
LS2 9JT
United Kingdom
Funders
Funder type
Industry
Funder name
Novartis Pharmaceuticals, USA
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2011 safety and tolerability results in http://www.ncbi.nlm.nih.gov/pubmed/21394500
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21995387
Publication citations
-
Safety and tolerability results
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, 127, 2, 429-438, doi: 10.1007/s10549-011-1429-y.
-
Results
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, , Breast-cancer adjuvant therapy with zoledronic acid., N. Engl. J. Med., 2011, 365, 15, 1396-1405, doi: 10.1056/NEJMoa1105195.