Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12606000293561
Ethics application status
Approved
Date submitted
10/07/2006
Date registered
11/07/2006
Date last updated
30/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
AZURE BR 2-03 - Adjuvant Zoledronic acid in patients with high risk localised breast cancer.
Scientific title
AZURE BR 2-03 - Does Adjuvant Zoledronic acid reduce recurrence in patients with high risk localised breast cancer?
Secondary ID [1] 276 0
VCOG BR 2-03
Universal Trial Number (UTN)
Trial acronym
AZURE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High risk, localised breast cancer 1267 0
Condition category
Condition code
Cancer 1353 1353 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For patients allocated to the investigational arm, zoledronic acid will be given intravenously at a dose of 4mg per treatment. The treatment schedule is every 3-4 weeks for the first 6 months with any chemotherapy, then 3 monthly for 2 years then 5 x 6 monthly infusions. Followup will continue for 5 years after the 5 year treatment period.
Intervention code [1] 1194 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Active

Outcomes
Primary outcome [1] 1844 0
To determine whether adjuvant treatment with 4mg zoledronic acid plus chemotherapy and/or endocrine therapy is superior to chemotherapy and/or endrocrine therapy alone in improving disease free survival.
Timepoint [1] 1844 0
Secondary outcome [1] 3241 0
Time to bone metastases as first recurrence
Timepoint [1] 3241 0
Secondary outcome [2] 3242 0
Time to bone metastases excluding first recurrence
Timepoint [2] 3242 0
Secondary outcome [3] 3243 0
Time to distant metastases
Timepoint [3] 3243 0
Secondary outcome [4] 3244 0
Overall survival
Timepoint [4] 3244 0
Secondary outcome [5] 3245 0
Reducing skeletal related events prior to development of bone metastases
Timepoint [5] 3245 0
Secondary outcome [6] 3246 0
Reducing skeletal related events following development of bone metastases
Timepoint [6] 3246 0
Secondary outcome [7] 3247 0
To assess the safety and toxicity of zoledronic acid in this clinical setting
Timepoint [7] 3247 0

Eligibility
Key inclusion criteria
Patients with Stage II/III primary breast cancer - Receiving or scheduled to receive neoadjuvant or adjuvant chemotherapy and/or endocrine therapy- Performance status Eastern Cooperative Oncology Group 0 or 1- Reliable and appropriate contraception. Patient must have given written informed consent prior to study specific procedures.
Minimum age
18 Years
Maximum age
Not stated
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Metastatic or recurrent breast cancer or a history of breast cancer (excluding ductal carcinoma in situ or lobular carcinoma in situ)- History of prior cancers within the preceding five years (including previous contralateral breast cancer)- History of diseases with influence on bone metabolism such as Paget's disease of the bone, primary hypothyroidism or osteoporosis requiring treatment at the time of study entry or within 6 months- Prior treatment with bisphosphonates within the past year- Serum creatinine > 1.5 x upper limit of normal- Known hypersensitivity to bisphosphonates- 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- Recent (within 4 weeks of study entry) or planned dental or jaw surgery (eg extractions, implants)- Pregnancy or breast feeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central UK based automated 24-hour telephone randomisation system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamically balanced, stratified by centre using minimisation software to ensure similar lymph node involvement, T stage, ER status, adjuvant systemic therapies, use of statins and menopausal status in the two arms
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/09/2003
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
3300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1483 0
Charities/Societies/Foundations
Name [1] 1483 0
Various cancer charities
Country [1] 1483 0
Funding source category [2] 1484 0
Commercial sector/Industry
Name [2] 1484 0
Novartis
Country [2] 1484 0
Primary sponsor type
Individual
Name
Prof Robert Coleman, The University of Sheffield, United Kingdom
Address
Country
United Kingdom
Secondary sponsor category [1] 1307 0
Government body
Name [1] 1307 0
Leeds Clinical Trial Research Unit, Leeds, United Kingdom
Address [1] 1307 0
Country [1] 1307 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2863 0
Alfred Hospital
Ethics committee address [1] 2863 0
Ethics committee country [1] 2863 0
Australia
Date submitted for ethics approval [1] 2863 0
Approval date [1] 2863 0
Ethics approval number [1] 2863 0
Ethics committee name [2] 2864 0
Austin Hospital
Ethics committee address [2] 2864 0
Ethics committee country [2] 2864 0
Australia
Date submitted for ethics approval [2] 2864 0
Approval date [2] 2864 0
Ethics approval number [2] 2864 0
Ethics committee name [3] 2865 0
Ballarat Oncology & Haematology
Ethics committee address [3] 2865 0
Ethics committee country [3] 2865 0
Australia
Date submitted for ethics approval [3] 2865 0
Approval date [3] 2865 0
Ethics approval number [3] 2865 0
Ethics committee name [4] 2866 0
Border Medical Oncology
Ethics committee address [4] 2866 0
Ethics committee country [4] 2866 0
Australia
Date submitted for ethics approval [4] 2866 0
Approval date [4] 2866 0
Ethics approval number [4] 2866 0
Ethics committee name [5] 2867 0
Box Hill Hospital
Ethics committee address [5] 2867 0
Ethics committee country [5] 2867 0
Australia
Date submitted for ethics approval [5] 2867 0
Approval date [5] 2867 0
Ethics approval number [5] 2867 0
Ethics committee name [6] 2868 0
Campbelltown, Hospital
Ethics committee address [6] 2868 0
Ethics committee country [6] 2868 0
Australia
Date submitted for ethics approval [6] 2868 0
Approval date [6] 2868 0
Ethics approval number [6] 2868 0
Ethics committee name [7] 2869 0
Concord Hospital
Ethics committee address [7] 2869 0
Ethics committee country [7] 2869 0
Australia
Date submitted for ethics approval [7] 2869 0
Approval date [7] 2869 0
Ethics approval number [7] 2869 0
Ethics committee name [8] 2870 0
Flinders Medical Centre
Ethics committee address [8] 2870 0
Ethics committee country [8] 2870 0
Australia
Date submitted for ethics approval [8] 2870 0
Approval date [8] 2870 0
Ethics approval number [8] 2870 0
Ethics committee name [9] 2871 0
Frankston Hospital
Ethics committee address [9] 2871 0
Ethics committee country [9] 2871 0
Australia
Date submitted for ethics approval [9] 2871 0
Approval date [9] 2871 0
Ethics approval number [9] 2871 0
Ethics committee name [10] 2872 0
Freemasons Hospital
Ethics committee address [10] 2872 0
Ethics committee country [10] 2872 0
Australia
Date submitted for ethics approval [10] 2872 0
Approval date [10] 2872 0
Ethics approval number [10] 2872 0
Ethics committee name [11] 2873 0
Geelong Hospital
Ethics committee address [11] 2873 0
Ethics committee country [11] 2873 0
Australia
Date submitted for ethics approval [11] 2873 0
Approval date [11] 2873 0
Ethics approval number [11] 2873 0
Ethics committee name [12] 2874 0
Liverpool Hospital
Ethics committee address [12] 2874 0
Ethics committee country [12] 2874 0
Australia
Date submitted for ethics approval [12] 2874 0
Approval date [12] 2874 0
Ethics approval number [12] 2874 0
Ethics committee name [13] 2875 0
Maroondah Hospital
Ethics committee address [13] 2875 0
Ethics committee country [13] 2875 0
Australia
Date submitted for ethics approval [13] 2875 0
Approval date [13] 2875 0
Ethics approval number [13] 2875 0
Ethics committee name [14] 2876 0
Mater Sydney Hospital
Ethics committee address [14] 2876 0
Ethics committee country [14] 2876 0
Australia
Date submitted for ethics approval [14] 2876 0
Approval date [14] 2876 0
Ethics approval number [14] 2876 0
Ethics committee name [15] 2877 0
Mercy Private Hospital
Ethics committee address [15] 2877 0
Ethics committee country [15] 2877 0
Australia
Date submitted for ethics approval [15] 2877 0
Approval date [15] 2877 0
Ethics approval number [15] 2877 0
Ethics committee name [16] 2878 0
Monash Medical Centre
Ethics committee address [16] 2878 0
Ethics committee country [16] 2878 0
Australia
Date submitted for ethics approval [16] 2878 0
Approval date [16] 2878 0
Ethics approval number [16] 2878 0
Ethics committee name [17] 2879 0
Peter MacCallum Cancer Centre
Ethics committee address [17] 2879 0
Ethics committee country [17] 2879 0
Australia
Date submitted for ethics approval [17] 2879 0
Approval date [17] 2879 0
Ethics approval number [17] 2879 0
Ethics committee name [18] 2880 0
Prince of Wales
Ethics committee address [18] 2880 0
Ethics committee country [18] 2880 0
Australia
Date submitted for ethics approval [18] 2880 0
Approval date [18] 2880 0
Ethics approval number [18] 2880 0
Ethics committee name [19] 2881 0
Queen Elizabeth
Ethics committee address [19] 2881 0
Ethics committee country [19] 2881 0
Australia
Date submitted for ethics approval [19] 2881 0
Approval date [19] 2881 0
Ethics approval number [19] 2881 0
Ethics committee name [20] 2882 0
Redcliffe Hospital
Ethics committee address [20] 2882 0
Ethics committee country [20] 2882 0
Australia
Date submitted for ethics approval [20] 2882 0
Approval date [20] 2882 0
Ethics approval number [20] 2882 0
Ethics committee name [21] 2883 0
Royal Melbourne Hospital
Ethics committee address [21] 2883 0
Ethics committee country [21] 2883 0
Australia
Date submitted for ethics approval [21] 2883 0
Approval date [21] 2883 0
Ethics approval number [21] 2883 0
Ethics committee name [22] 2884 0
Royal North Shore
Ethics committee address [22] 2884 0
Ethics committee country [22] 2884 0
Australia
Date submitted for ethics approval [22] 2884 0
Approval date [22] 2884 0
Ethics approval number [22] 2884 0
Ethics committee name [23] 2885 0
Royal Perth
Ethics committee address [23] 2885 0
Ethics committee country [23] 2885 0
Australia
Date submitted for ethics approval [23] 2885 0
Approval date [23] 2885 0
Ethics approval number [23] 2885 0
Ethics committee name [24] 2886 0
Royal Prince Alfred Hospital
Ethics committee address [24] 2886 0
Ethics committee country [24] 2886 0
Australia
Date submitted for ethics approval [24] 2886 0
Approval date [24] 2886 0
Ethics approval number [24] 2886 0
Ethics committee name [25] 2887 0
Sirriraj Hospital
Ethics committee address [25] 2887 0
Ethics committee country [25] 2887 0
THAILAND
Date submitted for ethics approval [25] 2887 0
Approval date [25] 2887 0
Ethics approval number [25] 2887 0
Ethics committee name [26] 2888 0
Songkla (Prince of)
Ethics committee address [26] 2888 0
Ethics committee country [26] 2888 0
THAILAND
Date submitted for ethics approval [26] 2888 0
Approval date [26] 2888 0
Ethics approval number [26] 2888 0
Ethics committee name [27] 2889 0
St John of God
Ethics committee address [27] 2889 0
Geelong, VIC
Ethics committee country [27] 2889 0
Australia
Date submitted for ethics approval [27] 2889 0
Approval date [27] 2889 0
Ethics approval number [27] 2889 0
Ethics committee name [28] 2890 0
St Vincent's Hospital
Ethics committee address [28] 2890 0
Ethics committee country [28] 2890 0
Australia
Date submitted for ethics approval [28] 2890 0
Approval date [28] 2890 0
Ethics approval number [28] 2890 0
Ethics committee name [29] 2891 0
Tweed Hospital
Ethics committee address [29] 2891 0
Ethics committee country [29] 2891 0
Australia
Date submitted for ethics approval [29] 2891 0
Approval date [29] 2891 0
Ethics approval number [29] 2891 0
Ethics committee name [30] 2892 0
Western Hospital
Ethics committee address [30] 2892 0
Ethics committee country [30] 2892 0
Australia
Date submitted for ethics approval [30] 2892 0
Approval date [30] 2892 0
Ethics approval number [30] 2892 0

Summary
Brief summary
The purpose of this study is to assess any benefits of adding a drug called ‘zoledronic acid’ (also known as ZometaTM) to the standard treatments for breast cancer. Zoledronic acid is one of a class of drugs that are known as bisphosphonates. In Australia, bisphosphonates are already approved to treat a number of medical conditions including osteoporosis (thinning of the bones), and in cancer patients to prevent pain and problems that occur when there has been spread of cancer to the bones. However, these drugs are not approved by Australian heatlh authorities for use in reducing the risk of breast cancer spreading to the bones. For this reason, ZometaTM is considered an investigational drug in this study.
There is evidence from earlier studies that bisphosphonates may prevent cancer spreading to the bones. This may be through their effects on bone, which make it more difficult for cancer cells to damage bone. Additionally, very strong bisphosphonates like zoledronic acid may have effects on the cancer cells themselves or help the drugs you are receiving to treat your cancer better.
This study was developed by doctors from the United Kingdom and Australia . The overall coordination of the trial is being done by the Clinical Trials and Research Unit at the University of Leeds, UK. The trial is being coordinated in Victoria by the Cancer Council Victoria who seek approximately 300 women to take part throughout Australia.
Approximately 3,300 women will take part in this study internationally, half of the women who take part will have the standard treatment that is normally given to treat breast cancer (this half are known as the “control group”), and the other half will have standard treatment plus zoledronic acid.
Women who choose to enter this trial may have treatments for 5 years and progress assessments for 10 years.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35533 0
Address 35533 0
Country 35533 0
Phone 35533 0
Fax 35533 0
Email 35533 0
Contact person for public queries
Name 10383 0
Deborah Howell
Address 10383 0
The Cancer Council Victoria
1 Rathdowne Street
Carlton Victoria 3053
Country 10383 0
Australia
Phone 10383 0
+61(0)39635 5179
Fax 10383 0
+61(0)39635 5410
Email 10383 0
[email protected]
Contact person for scientific queries
Name 1311 0
A/Prof Richard Bell
Address 1311 0
Andrew Love Cancer Centre
70 Swanston Street
Geelong Victoria 3220
Country 1311 0
Australia
Phone 1311 0
+61(0)35226 7855
Fax 1311 0
+61(0)35226 7290
Email 1311 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.