A 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: Breast cancer metastatic; MedDRA version: 11.0Level: LLTClassification code 10055113Term: <Manually entered code. Term in E.1.1>

• Registration Number: EUCTR2008-004171-21-CZ
• Lead Sponsor: PIERRE FABRE MEDICAMENT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-01
• Last Update Posted: 10 July 2015

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 (neoadjuvant treatment followed by adjuvant treatment will count as a single regimen).
- Prior treatments must have included both an anthracycline and a taxane.
- Patients must have received a minimum cumulative dose of anthracycline (to be applied to >or = 180 mg/m² of doxorubicin or>or=300 mg/m² of epirubicin)
or
be resistant to an anthracycline (to be applied to doxorubicin, epirubicin and liposomal doxorubicin) 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, to be considered resistant, a patient must have received at least 2 cycles of a taxane-based regimen.

- 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 3 weeks days prior to randomisation.
- Prior radiation therapy is allowed to < 30% of the bone marrow and must be completed at least 3 weeks before randomisation.
- Patient with measurable or non measurable disease according to revised RECIST guideline (version 1.1) (Eisenhaeur E, 2009).
- 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).
- Pa

Exclusion Criteria

- Patients with known or with clinical evidence of brain metastasis or leptomeningeal involvement.
- Patients with pulmonary lymphangitis or symptomatic pleural effusion (grade >or=2) that results in pulmonary dysfunction requiring active treatment.
- 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 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

Name	Time	Method
Main Objective: Primary objective: <br>- To compare between the 2 treatment arms the progression free survival.;Secondary Objective: Secondary objectives: <br>- To compare between the 2 arms, <br>1) the overall survival, <br>2) the response rate and the disease control rate, <br>3) the time to response and the duration of response, <br>4) the overall safety, <br>5) the impact of both treatments in the health-related quality of life.;Primary end point(s): The primary endpoint of this study is the progression free survival.