Phase III trial of IV vinflunine versus an alkylating agent in patients with metastatic breast cancer previously treated with or resistant to an anthracycline, a taxane, an antimetabolite, and a vinca-alkaloid (study L00070 IN 308 B0)

• Conditions: Metastatic breast cancer; MedDRA version: 15.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-011118-47-AT
• Lead Sponsor: PIERRE FABRE MEDICAMENT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-08-12
• Last Update Posted: 10 March 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 586

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 metastatic disease not amenable to curative surgery or radiotherapy
4. Patients must have received at least two prior chemotherapy regimens given for the treatment of locally recurrent and/or metastatic disease, excluding chemotherapy received in the neo/adjuvant setting
5. Prior treatments must have included an anthracycline, a taxane, an antimetabolite and a vinca-alkaloid (except vinflunine) in any combination or order
Patients may have received ixabepilone in countries where the drug has been registered.
6. Patients must be no longer candidate for anthracycline, taxane, antimetabolite and vinca-alkaloïd (except vinflunine) due to at least one of the following reasons:
- resistance to the drug defined as disease progression while on therapy or progression within 4 months of receiving last dose in the metastatic setting.
Only for anthracycline and taxane, a patient will also be considered as resistant if she relapsed within 12 months of last dose when given in the adjuvant or neoadjuvant setting.
- intolerance to the drug defined as the occurrence of severe myelotoxicity (febrile neutropenia, neutropenic infection, grade 4 neutropenia requiring G-CSF support, grade 4 thrombocytopenia or grade 3 thrombocytopenia requiring platelet transfusion) and/or the occurrence of grade = 3 non-haematological toxicity and / or the occurrence of grade 2 non-haematological toxicity lasting 14 days or more during one cycle of the drug,
- only for anthracycline, minimum cumulative dose of 180 mg/m2 for doxorubicin or 300 mg/m2 for epirubicin.
7. Patients must have received their last dose of vinca-alkaloid more than 4 months before randomisation
8. Patients may have been treated with anti-cancer hormonal therapy but are no longer considered candidate for hormone therapy
9. Patients with Her-2 positive tumours may have been treated with anti-Her 2 targeted therapy (trastuzumab, lapatinib) and must have discontinued at least 3 weeks prior to randomisation
10. Prior radiation therapy is allowed and must be completed at least 3 weeks before randomisation
11. Measurable or non measurable disease
12. Estimated life expectancy > or = 12 weeks
13. WHO performance status < or = 2
14. Age > or = 18 years and < or = 75 years
15. Adequate haematological function : absolute neutrophil count (ANC) >or = 1.5 x 109/l, platelets >or = 100 x 109/L, haemoglobin >or = 10g/dl. (Note that transfusion are not allowed during the month before first study drug administration, except if medically indicated)
16. Adequate hepatic function : transaminases 17. Adequate renal function : creatinine or = 50 ml/min
18. Women of childbearing potential must be using a medically accepted method of contraception (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 wi

Exclusion Criteria

1. Patients with pulmonary lymphangitis or symptomatic pleural effusion (grade >or = 2) that results in pulmonary dysfunction requiring active treatment or symptomatic ascites (grade >or= 2) requiring paracentesis.
2. Patients with meningeal carcinomatosis
3. Patients with central nervous system metastases unless the patient has completed local therapy, is stable for at least 4 weeks by CT-scan without evidence of cerebral oedema and has no requirement for corticosteroids or anticonvulsivants
4. Patients having received any other experimental or anti-cancer therapy within 30 days before randomisation except hormone therapy
5. Patients who participated in a prior vinflunine clinical trial
6. 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
7. Patients with pre-existing motor/sensory peripheral neuropathy of CTCAE version 3.0 grade > 1
8. History of severe hypersensitivity to vinca-alkaloids and/or alkylating agents or any contra indication to the study drugs
9. Known history of HIV infection
10. Pregnant or breast feeding women
11. 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
12. Prior history of high-dose chemotherapy with bone marrow transplantation or autologous stem cell infusion

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To compare the overall survival in patients treated with i.v. vinflunine versus those receiving an alkylating agent of physician’s choice.;Secondary Objective: - To compare between the 2 arms:<br>1) the progression-free survival, <br>2) the response rate and the disease control rate, <br>3) the duration of response and the disease control duration, <br>4) the time to response, <br>5) the overall safety, <br>6) the impact of both treatments on the health-related quality of life.;Primary end point(s): The primary efficacy endpoint will be overall survival defined as the time from randomisation to death or last follow-up.