Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting
Condition: Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II is studying the side effects and how well carboplatin and paclitaxel
      albumin-stabilized nanoparticle formulation when together with bevacizumab or trastuzumab
      before surgery works in treating patients with stage I-III breast cancer. Drugs used in
      chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation,
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Monoclonal antibodies, such as bevacizumab and trastuzumab, can
      block tumor growth in different ways. Some block the ability of tumor cells to grow and
      spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Giving more than one drug (combination chemotherapy) and monoclonal antibody therapy together
      before surgery may make the tumor smaller and reduce the amount of normal tissue that needs
      to be removed.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate 2 year progression-free survival in patients with breast cancer more than 1 cm
      and/or lymph node positive breast cancer treated with weekly Carboplatin/Nab-Paclitaxel (with
      trastuzumab in patients with HER2+ disease, and with bevacizumab in HER2-).

      II. To measure clinical response rates in patients treated in the neoadjuvant setting.

      III. To measure the microscopic pathological response rate of this regimen in patients
      treated in the neoadjuvant setting.

      IV. To measure the toxicity and delivered dose intensity of this regimen. V. To assess the
      association between microscopic pathologic complete response and clinical complete response
      at the primary tumor site in these patients.

      VI. To measure the outcome of patients treated with doxorubicin and cyclophosphamide with
      patients not treated with doxorubicin and cyclophosphamide.

      SECONDARY OBJECTIVES:

      I. Develop quantitative analysis methods to obtain pre-treatment tumor characteristic
      morphological, enhancement kinetic, and Choline metabolic parameters in breast cancer. Select
      an optimal set of features using the logistic regression analysis and the Artificial Neural
      Network (ANN) to predict pathologic complete remission (pCR) in HER-2 positive and negative
      arm.

      II. Investigate whether the early response patterns, analyzed using the percent tumor size
      changes, or changes in other lesion characteristic parameters, can be used to predict
      pathologic complete remission (pCR) in HER-2 positive and negative arm.

      III. Investigate whether combining the pre-treatment tumor characteristic parameters, and the
      early response pattern during the treatment course, can achieve a higher "area under the
      receiver operating characteristic (ROC) curve" (AUC) in prediction of pCR than those based on
      pre-treatment MRI characteristics or tumor response patterns alone.

      OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30
      minutes and carboplatin IV over 60 minutes once weekly for 12 weeks. Patients with
      HER2-positive disease receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and
      patients with HER2-negative disease receive bevacizumab IV over 30-90 minutes once every two
      weeks for 5 doses. Treatment continues in the absence of disease progression or unacceptable
      toxicity. Beginning 21-40 days later, patients undergo surgery.

      After completion of study treatment, patients are followed for 5 years.
    

Intervention name(s): Carboplatin; paclitaxel albumin-stabilized nanoparticle formulation; bevacizumab; trastuzumab; magnetic resonance imaging; therapeutic conventional surgery
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Optional correlative studies; Post-chemotherapy surgery for patients with a response or stable disease must take place no sooner than 21 days after last dose of Herceptin; and 40 days after last dose of bevacizumab to allow for normalization of blood counts
Other intervention name(s): Carboplatin Hexal; Carboplatino; CBDCA; Albumin-Stabilized Nanoparticle Paclitaxel; nab paclitaxel; nab-paclitaxel; nanoparticle albumin-bound paclitaxel; Nanoparticle Paclitaxel; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; anti-VEGF rhuMAb; recombinant humanized anti-VEGF monoclonal antibody; rhuMAb VEGF; anti-c-erB-2; MOAB HER2; monoclonal antibody c-erb-2; monoclonal antibody HER2; rhuMAb HER2; MRI; NMR imaging; NMRI; nuclear magnetic resonance imaging
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Carboplatin; Trastuzumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pre-operative; neo-adjuvant; triple negative; HER2 positive; hormone receptor positive; breast; Carboplatin; Nab-paclitaxel; Trastuzumab; Bevacizumab; Inflammatory