| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Woman with metastatic breast cancer |
|
| 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 | 10055113 |
| E.1.2 | Term | Breast cancer metastatic |
|
| 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 compare between the 2 treatment arms the progression free survival. |
|
| E.2.2 | Secondary objectives of the trial |
| To compare between the 2 arms, 1) the overall survival, 2) the response rate and the disease control rate, 3) the time to response and the duration of response, 4) the overall safety, 5) the impact of both treatments in the health-related quality of life. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Patients must give written informed consent (personally signed and dated) before completing any study-related procedure. 2. Women with histologically or cytologically confirmed carcinoma of the breast. 3. Documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy. 4. Patients must have received either one, two or three prior chemotherapy regimens including those administered in the neoadjuvant or adjuvant setting (sequential neoadjuvant/adjuvant treatment counting as one regimen.). 5. Prior treatments must have included both an anthracycline and a taxane. a) 6. Patients must have received a minimum cumulative dose of anthracycline (&#61619; 180 mg/m² of doxorubicin or &#61619; 300 mg/m² of epirubicin) or be resistant to an anthracycline according to the following criteria:Tumour progression while on anthracycline or within 4 months of the last anthracycline dose when given in the metastatic setting*; or b) Recurrence while on anthracycline or within 12 months of the last anthracycline dose when given in the adjuvant or neoadjuvant setting*. * Note: in addition to these criteria, to be considered resistant, a patient must have received at least 2 cycles of an anthracycline-based regimen 7. Patients must be resistant to taxane therapy according to the following criteria: a) Tumour progression while on taxane or within 4 months of last taxane dose when given in the metastatic setting** or, b) Recurrence while on taxane or within 12 months of the last taxane dose when given in the adjuvant setting or neoadjuvant setting**. ** Note: in addition to these criteria, patients taken off taxane therapy for reasons other than progression (e.g. toxicity) must have received a minimum of 3 cycles. 8. Prior anti-cancer hormone therapy is allowed but the patient must no longer be candidate for hormone therapy. The treatment must be terminated 2 weeks prior to randomization 9. Patients who have been treated with anti Her-2 targeted therapy (e.g. trastuzumab, lapatinib) must have discontinued therapy at least 4 weeks prior to randomisation. 10. Prior radiation therapy is allowed to < 30% of the bone marrow and must be completed at least 4 weeks before randomisation. 11. Patient must have measurable disease according to RECIST. 12. Adequate recovery from recent surgery. At least one week must have elapsed from the time of minor surgery, at least 3 weeks for major surgery. 13. Estimated life expectancy &#61619; 12 weeks. 14. Karnofsky performance score &#61619; 70 %. 15. Age &#61619; 21 years old. 16. Adequate haematological function. 17. Adequate hepatic function. 18 Adequate renal function. 19. ECG without clinically relevant abnormality 20. Patients on coumadin or warfarin must be on stable doses and have an International Normalized Ratio (INR) &#61603; 3 at the time of screening 21. Women of childbearing potential must be using a medically accepted method of contraception (e.g. barrier methods, intrauterine devices) to avoid pregnancy 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 in such a manner that the risk of pregnancy is minimised. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first treatment administration. |
|
| E.4 | Principal exclusion criteria |
| 1. Patients with known or with clinical evidence of brain metastasis or leptomeningeal involvement. 2. Inflammatory breast cancer without evidence of metastatic disease. 3. Patients having received any other experimental or anti-cancer therapy within 30 days before randomisation except hormone therapy. 4. History of second primary malignancy, except: bilateral breast carcinoma, in situ carcinoma of the cervix, adequately treated non melanomatous carcinoma of the skin, and other malignancy treated at least 5 years previously with no evidence of recurrence. 5. Patients 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. 6. Patients with pre-existing motor/sensory peripheral neuropathy of CTCAE version 3.0 grade > 1. 7. Patients having received > 3 regimens of chemotherapy 8. Prior therapy with capecitabine and/or vinca alkaloids (including vinflunine). 9. History of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or any contra indication to any of the study drugs. 10. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency. 11. Pregnant or breast feeding women. 12. Positive pregnancy test at inclusion. 13. Known history of HIV infection. 14. Inability to take and/or absorb oral medication including previous gastric surgery or any evidence of partial oesophageal, gastric, small or large bowel obstruction; gastrointestinal disorder that affect the absorption of capecitabine (malabsorption syndrome, 2/3 gastric resection and bowel resection). 15. Patients who have any 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 16. Prior bone marrow transplantation or autologous stem cell infusion following high-dose chemotherapy |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| progression free survival |
|
| 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 | 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) | 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| 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
|
| La fine dello studio e` definita come data ultima progressione osservata nel corso dello studio. Tuttavia allo scopo di ottenere una stima accurata della sopravvivenza globale, sara` richiesto un ulteriore periodo di follow-up di circa 18 mesi |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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