E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women 75 years or over with invasive, operable, moderate or strongly ER+ve, primary breast cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
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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 |
Primary objective: To compare surgery plus Arimidex with Arimidex alone in older women with ER+ve breast cancer in terms of overall survival in order to determine whether Arimidex alone provides anti-cancer efficacy which is not inferior to surgery plus adjuvant Arimidex therapy. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: To compare surgery plus Arimidex with Arimidex alone in older women with ER+ve breast cancer in terms of: • quality of life (QoL), in order to determine whether Arimidex alone is superior to surgery plus Arimidex in terms of QoL; • breast cancer specific survival, • failure-free survival and • local disease control, as secondary outcome measures to assess non-inferior anti-cancer efficacy of Arimidex alone; • health economic assessment;
Contralateral breast cancer rates, treatment related adverse events and skeletal related events will also be summarised.
Further objectives: Development of a patient selection tool based on: • Patient Characteristics • Disease Characteristics
Translational studies: To determine the molecular changes associated with the development of secondary Arimidex therapy resistance.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
full title: Early response biopsy sub-study
date and version: The early response biopsy sub-study is incorporated into the main protocol, therefore no separate date and version.
objectives: This sub-study aims to collect paired tumour samples from patients on the Arimidex alone arm in order to study early biological response markers to the Arimidex treatment. There is compelling evidence that early changes in tumour molecular profiles give important predictive information about tumour endocrine responsiveness (both degree of response and duration of response), which may predate any detectable clinical response. |
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E.3 | Principal inclusion criteria |
(1) Female and equal to or over 75 years of age. (2) Primary operable (TNM categories: T1, T2, T3, N0, N1, M0) invasive breast cancer (core biopsy or diagnostic incision biopsy proven). (3) Suitable for surgery. This may include local or general anaesthesia, and must remove all clinically palpable disease with clear pathological margins. Axillary staging for the clinically un-involved axilla will depend on local protocols and patient tolerance. (4) Moderate or strongly ER+ve, i.e. H Score equal to or greater than 100 or Allred Score equal to or greater than 5. (5) Ability to give informed consent. (6) Written informed consent. (7) Willing to complete the questionnaires for the additional trial evaluations. (8) Able to start trial treatment within 4 weeks of randomisation.
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E.4 | Principal exclusion criteria |
(1) Disease unsuitable for surgery, e.g. locally advanced or metastatic disease, extreme physical frailty precluding adequate surgery under either LA or GA. (2) Multifocal or bilateral invasive breast cancer. (3) Previous invasive breast cancer. (4) Previous or concurrent anti-oestrogen therapy for breast cancer. (5) Previous solid cancers other than breast in the last 10 years (except in the case of completely excised basal cell carcinoma/nonmelanomatous skin malignancy). (6) Inability to comply with study procedures. (7) History of severe renal impairment (creatinine clearance less than 20 ml/min). (8) History of moderate or severe hepatic disease (transaminases > 3 x ULN or bilirubin > 1.5 x ULN). (9) Known hypersensitivity to anastrozole or to any of the following excipients: Lactose Monohydrate, Povidone, Sodium Starch Glycollate, Magnesium Stearate, Hypromellose, Macrogol 300, or Titanium Dioxide. (10) Concurrent hormone replacement therapy (HRT) or therapy with any other oestrogen containing preparation. (11) Hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS) from randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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 | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life, Translational studies |
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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 | Yes |
E.8.2.3.1 | Comparator description |
The comparator arm of the trial is surgery plus Arimidex. |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 50 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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The end of the trial is defined as 5 years post-randomisation of the last patient entered, or death of all patients, whichever is sooner. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |