E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage II/III primary breast cancer, with T stage ≥ T1 |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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.
|
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Disease-free survival defined as the date of randomisation to death from any cause or recurrent disease |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 12 |