Vinflunine Plus Trastuzumab in Human Epidermal Growth Factor Receptor 2 (HER2neu) Over-Expressing Metastatic Breast Cancer
Condition: Breast Neoplasms; Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Vinflunine; Trastuzumab
Intervention description: Novel second generation vinca alkaloid; Anti-HER2 monoclonal antibody
Intervention MeSH terms: Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Neoplasms; Breast Cancer; Vinflunine; Vinca Alkaloid; Javlor

Summary:

      This research study involves the anti-cancer medication trastuzumab and the investigational
      drug vinflunine. The purpose of this trials is to see if trastuzumab and vinflunine used in
      combination or vinflunine alone is effective in the treatment of metastatic breast cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed breast cancer with
             metastatic disease. Patients without pathologic or cytologic confirmation of
             metastatic disease should have unequivocal evidence of metastasis using the Response
             Evaluation Criteria in Solid Tumors (RECIST) criteria.

          -  The human epidermal growth factor receptor 2 (HER2) status of the tumor will be used
             to stratify patients. Tumors that are HER2 FISH+ will receive vinflunine and
             trastuzumab. Patients with tumors which are HER2 FISH negative or if the HER2 status
             is unknown/not performed will remain on study and will receive single agent
             vinflunine.

          -  Patients must have measurable disease not directly irradiated as per RECIST criteria.

          -  Measurable disease- is defined as at least one lesion that can be accurately measured
             in at least one dimension (longest diameter to be recorded) as >20 mm with
             conventional techniques or as >10 mm with spiral CT scan.

          -  Prior Therapy: Patients must not have received prior chemotherapy in the metastatic
             breast setting. Patients who have not received prior anthracyclines or taxanes should
             be considered for these agents. Patients may have received prior chemotherapy and/or
             hormonal therapy for early stage breast cancer. The chemotherapy regimen may have
             included an anthracycline and/or a taxane as long as it has been > 6 months since
             completion of the regimen. Adjuvant trastuzumab is allowed. Patients may have received
             prior radiation therapy in either the metastatic or early stage setting as long as
             <25% of the bone marrow has been treated. Prior radiation to the whole pelvis is not
             allowed. Radiation therapy must be completed at least 7 days prior to study
             registration, and all radiation related toxicities must be resolved to grade ≤ 1
             before patient is eligible for study inclusion. Patients may have received any number
             of hormonal therapies in the neo-adjuvant, adjuvant or metastatic setting.

          -  Age >18 years.

          -  Life expectancy of > 6 months.

          -  Eastern Cooperative Oncology Group (ECOG) performance status <2.

          -  Patients must have normal organ and marrow function. Laboratory tests should be
             completed within 14 days prior to starting study treatment. Only for patients who will
             be receiving trastuzumab, a left ventricular ejection fraction (LVEF) may be
             determined by either echocardiography or multigated acquisition (MUGA) scan, and
             should be obtained within 4 weeks prior to starting study treatment.

          -  Fertility/reproduction. Patients must not be pregnant, expect to become pregnant or
             conceive a child from time of first signing study consent until at least 12 weeks
             after last dose of study treatment.

        Exclusion Criteria

          -  Patients who have received prior vinca alkaloid chemotherapy are not eligible unless
             treatment was completed > 5 years ago.

          -  Patients in which the HER2 status is unknown or is FISH negative will not receive
             trastuzumab but are eligible for treatment with single agent vinflunine.

          -  Patients that have received prior chemotherapy for metastatic breast cancer.

          -  Patients receiving trastuzumab must have received a cumulative dose of doxorubicin
             less than 360mg/m2, and/or an epirubicin cumulative dose less than 720mg/m2 for study
             entry.

          -  Patients with known leptomeningeal carcinomatosis are excluded from this clinical
             trial

          -  History of grade 3 or 4 allergic reactions attributed to trastuzumab.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study

          -  History of other non-breast cancer malignancy except for carcinoma in situ of the
             cervix or non-melanoma skin cancer, or in patients with greater than a 5-year disease
             free interval from a prior malignancy.

          -  Patients who have received prior chemotherapy for early stage breast cancer with the
             completion of the regimen being < 6 months will not be eligible.