A randomised study to determine whether zoledronic acid adds to the benefits of chemotherapy and/or hormone therapy in the treatment of women with breast cancer. –AZURE STUDY– - AZURE

• Register: EUCTR
• Last refreshed on: 6 February 2017
• Main ID: EUCTR2004-000608-42-ES
• Date of registration: 16/11/2004
• Prospective Registration: Yes
• Primary sponsor: University of Sheffield
• Public title: A randomised study to determine whether zoledronic acid adds to the benefits of chemotherapy and/or hormone therapy in the treatment of women with breast cancer. –AZURE STUDY– - AZURE
• Scientific title: A randomised study to determine whether zoledronic acid adds to the benefits of chemotherapy and/or hormone therapy in the treatment of women with breast cancer. –AZURE STUDY– - AZURE
• Date of first enrolment: 19/11/2004
• Target sample size: 3300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000608-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion criteria:
•Female patients with Stage II / III primary breast cancer, with T stage = T1
•Patients should be receiving / scheduled to receive chemotherapy and/or endocrine therapy
•Patients receiving neo-adjuvant therapy
-must have either tumour size of >5cm (T3) or features of locally advanced disease (T4) involvement
-should be scheduled to proceed to definitive surgery$ and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy
-time between commencement of neoadjuvant treatment and planned start date of study drug should be equal or less than 30 days
•Patients receiving adjuvant therapy
-must have undergone complete primary tumour resection and treatment of the axillary lymph nodes, without any prior neoadjuvant therapy
-must have evidence of lymph node involvement
-time between definitive surgery$ and planned start date of study drug should be equal or less than 60 days
•Performance status: Karnofsky Index = 60% or ECOG 0 and 1
•Women of childbearing potential must be using a reliable and appropriate method of contraception
•Age = 18 years
•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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Metastatic or recurrent breast cancer or a history of breast cancer (aside from DCIS or LCIS) prior to the currently diagnosed case
•History of prior cancers within the preceding five years (including previous contralateral breast cancer), aside from non-melanomatous skin cancer or carcinoma in situ of the uterine cervix treated with curative intent
•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 six months
•Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol
•Prior treatment with bisphosphonates within the past year
•Serum creatinine > 1.5 x Upper Limit of Normal
•Known hypersensitivity to bisphosphonates
•Pregnancy or breast-feeding
•Use of other investigational drugs in the 30 days prior to study entry





Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Stage II/III primary breast cancer, with T stage = T1

Intervention(s)

Trade Name: ZOMETA
Product Name: ZOMETA
Product Code: None
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Zoledronic Acid
CAS Number: ZOL446
Current Sponsor code: CGP42446, ZOL446
Other descriptive name: Zoledronate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.8-

Primary Outcome(s)

Main Objective: 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 Objective: To determine whether zoledronic acid with chemotherapy and/or endocrine therapy is superior to chemotherapy and/or endocrine therapy alone in terms of:
•time to bone metastases as first recurrence
•time to bone metastases per se
•time to distant metastases
•overall survival
•reducing skeletal-related events* prior to development of bone metastases
•reducing skeletal-related events* following development of bone metastases.

Additional secondary objectives are:
•to assess the safety and toxicity of zoledronic acid in this clinical setting
•to evaluate the influence of prognostic factors, such as ER/PR status, TNM stage, tumour grade, HER2/neu (if available) and menopausal status on treatment outcome

* Defined as: fractures, spinal cord compression, radiation therapy to bone, surgery to bone and hypercalcaemia

Primary end point(s): Disease-free survival defined as the date of randomisation to death from any cause or recurrent disease

Secondary ID(s)

ISRCTN79831382/NovartisCZOL446G2408

ISRCTN79831382