Trastuzumab, Ixabepilone, and Carboplatin in Treating Patients With HER2/Neu-Positive Metastatic Breast Cancer
Condition: HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms; Breast Neoplasms, Male
Intervention: trastuzumab; ixabepilone; carboplatin; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Correlative studies
Intervention MeSH terms: Carboplatin; Trastuzumab; Epothilone B; Epothilones
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving trastuzumab together with ixabepilone and
      carboplatin works in treating patients with HER2/neu-positive metastatic breast cancer.
      Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or
      deliver tumor-killing substances to them without harming normal cells. Drugs used in
      chemotherapy, such as ixabepilone and carboplatin, work in different ways to stop tumor cells
      from dividing so they stop growing or die. Combining trastuzumab with ixabepilone and
      carboplatin may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically confirmed adenocarcinoma of the breast which is
             metastatic and is known to overexpress HER2/neu who have received no prior
             chemotherapy for metastatic breast cancer; prior hormonal therapy for metastatic
             disease is allowed; NOTE: for this protocol, HER2 overexpression will be defined as 3+
             HER2 positivity as measured by immunohistochemistry using the HercepTest (DAKO) or
             HER2 gene amplification as measured by fluorescent in-situ hybridization (FISH, e.g.
             Vysis); representative diagnostic tissue must be submitted for central diagnostic
             review

          -  Patients must not be pregnant or breast feeding because of the teratogenic potential
             of these drugs; it is recommended that all females of childbearing potential have a
             blood test or urine study within 2 weeks prior to registration to rule out pregnancy;
             women of childbearing potential and sexually active males must be strongly advised to
             use an accepted and effective non-hormonal method of contraception

          -  Patients must have at least one objective measurable disease parameter; baseline
             measurements and evaluations using RECIST criteria guidelines must be obtained within
             4 weeks prior to registration to the study; NOTE: all areas of disease should be
             recorded and followed

          -  Patients must have an ECOG performance status of 0 or 1

          -  Patients must be disease free of prior malignancy for >= 5 years with the exception of
             curatively treated basal cell carcinoma or squamous cell carcinomas of the skin or
             carcinoma in situ of the cervix

          -  Patients must not have a history of untreated brain metastasis or brain metastasis
             currently undergoing radiation; patients with brain metastasis representing the sole
             site of disease are not eligible for this study; patients with previously treated
             brain metastasis who have responded to brain radiotherapy and/or surgery and continue
             in response are eligible provided the brain is not the only site of measurable disease

          -  Patients must not have peripheral neuropathy of any grade

          -  Patients must not have a history of prior severe (grade 3 or 4) hypersensitivity
             reaction to a drug formulated in polyoxyethylated castor oil (Cremophor EL)

          -  Patients must have left ventricular ejection fraction by MUGA scan or echocardiogram
             that is at or above the lower institutional limits of normal obtained within 6 weeks
             prior to registration

          -  Patients must not have a history of New York Heart Association class 3 or 4 heart
             failure

          -  Serum creatinine =< 1.5 mg/dl

          -  Granulocytes >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  SGOT(AST) and SGPT(ALT) =< 1.5 x upper limit of normal (unless liver is involved by
             tumor, in which case SGOT(AST) and SGPT(ALT) can be =< 2.0 x upper limit of normal)

          -  Patients must have no history of prior therapy with trastuzumab (Herceptin),
             Ixabepilone (BMS-247550) or carboplatin for metastatic disease; patients who develop
             metastatic disease =< 6 months after completing adjuvant trastuzumab (Herceptin),
             paclitaxel, docetaxel, carboplatin, or Ixabepilone (BMS-247550) are considered to have
             had prior therapy for metastatic disease and are excluded from study participation

          -  Patients must not have received a cumulative dose of doxorubicin of greater than 360
             mg/m^2 or epirubicin of greater than 640 mg/m^2

          -  Concurrent use of hormonal therapy is not permitted; concurrent radiation therapy is
             not permitted; hormonal therapy must have been discontinued >= 1 week prior to
             registration; radiation therapy must have been completed >= 2 weeks prior to
             registration

          -  Patients may have had prior radiation therapy, but the previously irradiated tumors
             cannot be used to assess a clinical response; patients will not be eligible if they do
             not have other areas of measurable disease; an exception will be given for patients
             who have had tumor recurrence in an area that received adjuvant radiation treatments,
             such as the axilla or chest wall