Condition category
Cancer
Date applied
20/08/2003
Date assigned
20/08/2003
Last edited
08/11/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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 Paget’s 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

Sponsor information

Organisation

The University of Sheffield (UK)

Sponsor details

Western Bank
UK
Sheffield
S10 2TN
United Kingdom

Sponsor type

University/education

Website

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

Results - basic reporting

Publication summary

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

  1. 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.

  2. 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.

Additional files

Editorial Notes