E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of patients with unresectable, locally recurrent or metastatic breast cancer after prior anthracycline-based adjuvant chemotherapy or if contraindicated, a non-anthracycline based chemotherapy. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 show that the vinflunine plus gemcitabine test arm is non inferior to the paclitaxel plus gemcitabine control arm in terms of progression-free survival. If non inferiority is claimed after this first test, a second test will be performed in order to show that the vinflunine plus gemcitabine arm is superior to the paclitaxel plus gemcitabine arm in terms of progression-free survival. |
|
E.2.2 | Secondary objectives of the trial |
To compare between the 2 treatment arms: - the tumour response rate, - the duration of response, duration of disease control, time to treatment failure and time to first response, - the overall survical, - the safety profile, - the health-related quality of life through a QOL questionnaire. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient must given written informed consent (personnaly dated and signed) - Age between 18 and 75 years old - Woman with histologically or cytologically confirmed carcinoma of the breast - Woman of chilbearing potential must be using a medically accepted method of contraception to avoid pregancy during the 2 months preceding the start of study treatment, throughout the study period and for up to 3 months after the last dose of study treatment. Woman of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first treatment administration -Documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy. - Patient with eiter HER-2 negative disease assessed by IHC 0-1+ or FISH/CISH negative, on the primary tumour or on metastatic site, or HER-2 status unknown, provided that a tumour sample is available for retrospective review, if relevant. - Patient must have received a prior neo-adjuvant and/or adjuvant anthracycline based chemotherapy ( or if contraindicated, a non-anthracycline based chemotherapy) with or without a taxane. The disease free interval from completion of the prior chemotherapy must be more than 12 months. - Prior hormone therapy is allowed either in the neoadjuvant and/or adjuvant setting and in the metastatic setting provided that there is a documented progression of the disease ant the treatment must be terminated prior to randomisation. - Prior radiation therapy allowed to inferior25% of the bone marrow and must be completed at least 4 weeks before randomisation. - Patient with measurable or non-measurable lesion usong the RECIST guidelines. - Estimated life expectancy superior or equal to 12 weeks. - Karnofsky performance score > or = 70% - Adequate haematological function (within 7 days before first study treatment): ANC >or=1,5 x 109/L, platelet count >or =100 x 109/L and haemaglobin >or=10 g/dL. - Adequate hepatic function (within 7 days before first study treatment): Total bilirubin <or=1,5 x ULN, AST and ALT <or=2,5 x ULN or <or= 5 x ULN in case of liver metastases, alkaline phospatase <or=5 x ULN. - Adequate renal function (within 7 days before first treatment administration): creatinine level within normal values or, in case of creatinine level > ULN, calculated creatinine clearance >or= 60 mL/min according to Cockroft-Gault formula. - ECG without clinically relevant modification (within 7 days before first treatment administration). |
|
E.4 | Principal exclusion criteria |
- Patient having received previous chemotherapy for metastatic disease or having progressed while on adjuvant chemotherapy or within 12 months from completion of adjuvant chemotherapy. - Patient with known or with clinical evidence of brain metastatic or leptomeningeal involment. - Inflammatory breast cancer without evidence of metastatic disease. - Patient having received any other experimental or anti-cancer therapy within 30 days before randomisation, except hormone therapy - History of second primary malignancy, except: bilateral breast carcinoma, in situ carcinoma of the cervix, adequately treated non melanomatous carcinoma of the skin, or other malignancy treated at least 5 years previously with no evidence of recurrence. - Patient having as the sole tumour lesion, any of the following: malignant effusion, lymphangitis, cystic lesion, bone lesion and any other lesion that is not assessed by imaging techniques or colour photography. - Patient with pre-existing motor or sensory peripheral neuropathy of CTCAE version 3.0 grade >1. - History of severe hypersensitivity to vinca alkaloids and/or gemcitabine and/or taxanes or any contraindication to any of the study drugs. - Pregnant or breast feeding woman. - Patient who had a serious, concurrent uncontrolled medical disorder especially uncontrolled hypercalcaemia, congestive heart failure, uncontrolled high-risk hypertension, arrhythmia, angina pectoris or previous history of myocardial infarction within 6 months prior to randomisation. - Prior bone marrow transplantation or autologous stem cell infusion following high-dose chemotherapy. - Prior therapy with gemcitabine and/or vinca alkaloids. - Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; and patients under guardianship (e.g. individuals who are not able to freely give their informed consent). These conditions should be assessed with the patient before randomisation.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
- Progression-free survival will be calculated from the date of randomisation until the date of progression or death (whatever the reason of 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 | No |
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 | Yes |
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) | Yes |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 113 |
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 | 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 | 6 |
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 | 6 |
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 |