E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal women with primary invasive breast cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
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 |
The primary objective of the current study is to evaluate statin induced effects on tumour proliferation response. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- To evaluate the treatment predictive role of HMG-CoA reductase expression. - To evaluate the relation between blood lipid profile and statin induced tumour inhibition. - To evaluate the the relation between statin induced tumour effects and other proteins synthesized in the mevalonate pathway. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Women with primary breast cancer who are candidates for radical surgery. • Breast tumours clinically ≥ 15 mm, Nx, M0. • Breast tumours identified on mammography and verified on fine needle aspiration. • Age > 18 years. • Postmenopausal women. Postmenopausal status defined as ≥ 1 year since last menstruation in women with no medical history of hysterectomy or women with a medical history of oophofectomy. • Performance status of ECOG ≤ 1. • Laboratory requirements at the day of diagnosis (t1-): Prior to inclusion a normal renal (serum creatinine) and hepatic (transaminases) function (within normal limits) estimated in blood samples is required. • Prior to patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
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E.4 | Principal exclusion criteria |
• ongoing cholesterol lowering therapy (statins, fibrates, ezetimibe). • prior breast cancer treatment. • current HRT. • known liver disease. • history of hemorrhagic stroke. • psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions will be discussed with the patient before registration in the trial. • history of allergic reactions attributed to compounds of similar chemical or biological composition to atorvastatin.
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E.5 End points |
E.5.1 | Primary end point(s) |
Tumour proliferation will be determined by immunohistochemical expression of Ki67 (monoclonal antibody, 1:200 MIB-1, Dako, Denmark) in the core biopsy (t1) and in breast cancer tissue obtained from the operated lump (t2). Ki67 will be assessed as the percentage of positively stained cells among a minimum of 1000 malignant cells (fraction as a continuous variable). A relative change of 35% between t1 and t2 will be regarded as clinically significant result. Prior to statistical analyses and final decision on the clinically relevant reduction in proliferation rate (Ki67), the expected normal variability of the investigated biological markers between biopsy specimens and surgical specimens with approximately two weeks interval in untreated patients, should be estimated in a retrospectively collected cohort of postmenopausal breast cancer cases.
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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 | No |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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 | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |