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Ensayo clínico en fase III de vinflunina más capecitabina frente a sólo capecitabina en pacientes con cáncer de mama avanzado previamente tratados con o resistentes a una antraciclina y que sean resistentes a taxanosA phase III trial of vinflunine + capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with or resistant to an anthracycline and who are taxane resistant

Conditions
Cáncer de mama metastásicoBreast cancer metastatic
MedDRA version: 11.1Level: LLTClassification code 10055113Term: <Manually entered code. Term in E.1.1>
Registration Number
EUCTR2008-004171-21-ES
Lead Sponsor
PIERRE FABRE MEDICAMENT
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Female
Target Recruitment
764
Inclusion Criteria

·
- Patients must give written informed consent (personally signed and dated) before completing any study-related procedure.
- Women with histologically or cytologically confirmed carcinoma of the breast.
- Documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy.
- 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.).
- Prior treatments must have included both an anthracycline and a taxane.
- Patients must have received a minimum cumulative dose of anthracycline (>or = 180 mg/m² of doxorubicin or ³ 300 mg/m² of epirubicin) or be resistant to an anthracycline according to the following criteria:
a) 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

- 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.

- 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 randomisation.
- Patients who have been treated with anti Her2 targeted therapy (e.g. trastuzumab, lapatinib) must have discontinued therapy at least 4 weeks days prior to randomisation.
- Prior radiation therapy is allowed to < 30% of the bone marrow and must be completed at least 4 weeks before randomisation.
- Patient must have measurable disease according to RECIST.
- Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of minor surgery, at least 3 weeks for major surgery.
- Estimated life expectancy >or= 12 weeks.
- Karnofsky performance score >or= 70 %.
- Age >or= 21 years old.
- Adequate haematological function as defined by absolute neutrophil count (ANC) >or= 1.5 x 109/L, platelet count >or= 100 x109/L and hemoglobin >or= 10 g/dL (within 7 days before first study treatment).
- Adequate hepatic function as defined by: total bilirubin - Adequate renal function as defined by a calculated creatinine clearance >or= 50 mL/min according to Cockroft-Gault formula (ml/min) = [(0.85)(140-age)(weight)]/[(0.81)(SrCr µmol/L)] (within 7 days before first treatment administration).
- ECG without clinically relevant abnormality (within 7 days before first treatment administration).
- Patients on coumadin or warfarin must be on stable doses and have an International Normalized Ratio (INR) - Women

Exclusion Criteria

- Patients with known or with clinical evidence of brain metastasis or leptomeningeal involvement.
- Inflammatory breast cancer without evidence of metastatic disease.
- Patients 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, and other malignancy treated at least 5 years previously with no evidence of recurrence.
- 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.
- Patients with pre-existing motor/sensory peripheral neuropathy of CTCAE version 3.0 grade > 1.
- Patients having received > 3 regimens of chemotherapy
- Prior therapy with capecitabine and/or vinca alkaloids (including vinflunine).
- History of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or any contra indication to any of the study drugs.
- Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency.
- Pregnant or breast feeding women.
- Positive pregnancy test at inclusion.
- Known history of HIV infection.
- 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).
- 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
- Prior bone marrow transplantation or autologous stem cell infusion following high-dose chemotherapy.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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