Phase III Study of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer
Condition: Malignant Neoplasm of Breast
MeSH terms: Neoplasms; Breast Neoplasms
Intervention: vinflunine; Capecitabine
Intervention description: intravenous administration day 1 once every 3 weeks, 280 mg/m²; Arm A : 1650 mg/m² Arm B : 2500 mg/m²
Intervention MeSH terms: Capecitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 112.0
Sex: Female
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      Options for the treatment of patients who have progressed after an anthracycline and a taxane
      are limited. Capecitabine currently has a role in this setting, yet as many as 80% of
      patients do not respond to this treatment and those who respond eventually develop clinical
      resistance.

      The antitumour activity of vinflunine has been demonstrated in patients with breast cancer
      after exposure to anthracycline and to taxane.

      Vinflunine plus capecitabine has been shown to be a feasible combination for patients
      previously treated with an anthracycline and a taxane. Each drug in combination can be
      administered at efficacious doses.

      This population has few therapeutic options with established clinical benefit. The
      development of a new regimen and potential new standard of care for this group is important.

        -  Primary objective:

           • to compare in patients with advanced breast cancer pretreated with anthracycline and
           taxane the efficacy of the combination of vinflunine and capecitabine with capecitabine
           alone, in terms of progression-free survival.

        -  Secondary objectives:

             -  to evaluate the response rate, the time to response and the duration of response in
                both arms

             -  to compare the disease control rate between arms

             -  to evaluate the duration of disease control in both arms

             -  to evaluate the overall survival in both arms

             -  to evaluate safety

      Methodology This multicentre, open-label, randomised, Phase III study will enrol a total of
      334 patients with advanced breast cancer who have previously been treated with an
      anthracycline and a taxane. Patients will be randomised in a 1:1 ratio to receive VFL plus
      capecitabine (Arm A) or capecitabine alone (Arm B).
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Written informed consent

          2. Histologically or cytologically confirmed Her-2 negative carcinoma of the breast

          3. Documented locally recurrent or metastatic disease not amenable to curative surgery or
             radiotherapy

          4. One, two or three prior chemotherapy regimens including those administered in the
             neoadjuvant or adjuvant setting. At least one of the regimens must have been given for
             the treatment of advanced disease.

          5. Prior treatment must have included both an anthracycline and a taxane. minimum
             cumulative dose of 180 mg/m² of doxorubicin or of 300 mg/m² of epirubicin

          6. Documented progression on or within 12 months of the most recent chemotherapy.

          7. Prior hormone therapy is allowed

          8. Prior radiation therapy is allowed to less than 30% of the bone marrow

          9. LMeasurable or non measurable disease defined according to RECIST V1.1

         10. Adequate recovery from recent surgery

         11. Estimated life expectancy superior or equal of 12 weeks

         12. KPS equal or superior to 70%

         13. Age equal or superior to 21 years and < 80 years

         14. ANC) equal or superior to 1.5 x 109/L, platelet count equal or superior to 100 x109/L
             and haemoglobin > 10 g/dL.

         15. Bilirubin inferior or equal to 1.5 x upper limit of normal (ULN), AST and ALT inferior
             or equal to 2.5 x ULN or inferior or equal to 5 x ULN in the case of liver metastases,
             alkaline phosphatase inferior or equal to 5 x ULN.

         16. Calculated creatinine clearance superior or equal to 50 mL/min

         17. Normal ECG

         18. Patients on coumadin or warfarin must be on stable doses and INR inferior or equal to
             3

         19. Women of childbearing potential must be using a medically accepted method of
             contraception. Women of childbearing potential must have a negative serum or urine
             pregnancy test within 72 hours prior to first treatment administration.

         20. Absence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule; those
             conditions should be assessed with the patient before registration in the trial.

        EXCLUSION CRITERIA

          1. Known or with clinical evidence of brain metastasis or leptomeningeal involvement.

          2. Pulmonary lymphangitis or symptomatic pleural effusion (grade > 2) that results in
             pulmonary dysfunction requiring active treatment.

          3. Patients having received any other experimental drug or chemotherapy within 30 days

          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. Pre-existing motor/sensory peripheral neuropathy of CTCAE version 3.0 grade >1

          6. Patients having received > 3 regimens of chemotherapy

          7. Prior therapy with capecitabine and/or vinca-alkaloids

          8. History of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or
             any contra indication to any of the study drugs

          9. Known or suspected DPD

         10. Pregnant or lactating; With positive pregnancy test at inclusion

         11. Female of childbearing potential who is unwilling or unable to use a medically
             accepted method to avoid pregnancy during the 2 months preceding the start of study
             treatment, throughout the study period and at least 3 months following the last dose
             of study treatment

         12. Known history of HIV infection

         13. Inability to take and/or absorb oral medication

         14. 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.

         15. Prior BMT or autologous stem cell infusion following high-dose chemotherapy.