E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastases breast cancer in women already treated with aromatase inhibitors. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
|
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 the percentage of progression free survival after a 6-month monotherapy of Estramustine in patients with HER2-/RH+ breast cancer progressing after having already undergone either a first line adjuvant treatment by aromatase inhibitors (AI) |
|
E.2.2 | Secondary objectives of the trial |
- To describe the risks of thrombosis by the analysis of the following biomarkers : D-Dimer, prothrombin fragment 1+2, von Willebrand factor, fibrinogen, Chain Reaction Protein (CRP)
- To describe the clinical benefit of estramustine every 2 months during the one-year patient follow-up (RECIST criteria)
- To describe the correlation between the answer rate and the decrease of the following biomarkers: LDH, ACE and CA 15-3 every 2 months during the one-year patient follow-up
- To evaluate tolerance of estramustine and tamoxifene treatments every 2 months during the one-year patient follow-up
- To analyse the proportion of patients developing thromboembolic events in the 2 groups every month every during the one-year patient follow-up
- To evaluate patient's quality of life (questionnaire EORTC QLQ-C30 and EORTC QLQ-BR23) every 4 months every during the one-year patient follow-up
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Post-menopausal women or women receiving LHRH analogs • Histologically confirmed metastatic breast cancer RH+ • Measurable metastatic breast cancer (modified RECIST criteria) or not mesurable but evaluable • Recurrence: - being treated with aromatase inhibitors (AIs) - less than one year after adjuvant treatment by AIs - after progression of the metastatic cancer in patients receiving AIs following positive response during at least 6 months • Performance index ≤ 2 (OMS) • Haematological test: polynuclear neutrophiles ≥ 1.5 × 109 /L, haemoglobin ≥ 9 g/dL, blood platelet ≥ 100 × 109 /L • Hepatic function: albumin ≥ 2.5 g/dL, serum bilirubin ≤ 1.5 × N (except if Gilbert’s Syndrome) , aminotransferases ≤ 3 × N (≤ 5 × N if hepatic metastases) • Renal function: serum creatinine ≤ 1.5 mg/dL or clearance of creatinine ≥ 40 ml/min • Women without endometrial pathology • Patient who agrees, according to the investigator, to comply with the study requirements • Signed informed consent |
|
E.4 | Principal exclusion criteria |
• Women aged < 18 • Pre-menopausal, pregnant or lactating females • Patient who should exclusively be treated by chemotherapy • Women previously treated with chemotherapy but not by AIs • Women previously treated by tamoxifene for their metastatic breast cancer • HER2+ tumour • Concurrent anti-cancer treatment (chemotherapy, surgery, immunotherapy, biological therapy and tumour embolism) • Concurrent treatment with protocol-defined prohibited medications • Malabsorption syndrome , significant digestive dysfunction, gastrectomy, jejunectomy, hemorrhagic recto colon • Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent) • Any pathology, including severe psychiatric or psychologic disease that may harm patient’s safety or participation in the study • Serious or not cured or unstable toxicity due to the administration of another drug being involved in clinical trials • Uncontrolled cardiovascular pathologies • Previous cardiovascular disease of type deep vein thrombosis or pulmonary embolism recorded within one year before the inclusion date • Active uncontrolled infection • Risk of thromboembolic events such as: - personal history of any thromboembolic event - antiphospholipid antibody - family history of thrombophilia • Participation to a clinical trial at least 4 weeks prior the start of the study |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients in progression-free survival (PFS) after a 6-month treatment is the main judgement criterion. The PFS is defined as the duration of objective response or stabilisation of the disease according to the Recist criteria. The following events shall be considered as progressive : - Relapse - Treatment intolerance leading to stop the treatment - Death |
|
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 | 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 | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 19 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 0 |
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 |