Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting

• Clinical complete response in the neoadjuvant setting [ Time Frame: Up to 5 years ]
  Defined as normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange. The 95% confidence interval (CI) will be computed.
• Microscopic pCR in the neoadjuvant setting [ Time Frame: Up to 5 years ]
  Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed.
• Toxicity of the combinations in HER2 positive and HER2 negative breast cancer assessed using the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 [ Time Frame: Up to 5 years ]
  The frequency of toxicities will be recorded.

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.

• 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

• Drug: Carboplatin
  Given IV
  Other Names:

  • Carboplatin Hexal
  • Carboplatino
  • CBDCA
• Drug: paclitaxel albumin-stabilized nanoparticle formulation
  Given IV
  Other Names:

  • Albumin-Stabilized Nanoparticle Paclitaxel
  • nab paclitaxel
  • nab-paclitaxel
  • nanoparticle albumin-bound paclitaxel
  • Nanoparticle Paclitaxel
• Drug: bevacizumab
  Given IV
  Other Names:

  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • anti-VEGF rhuMAb
  • recombinant humanized anti-VEGF monoclonal antibody
  • rhuMAb VEGF
• Drug: trastuzumab
  Given IV
  Other Names:

  • anti-c-erB-2
  • MOAB HER2
  • monoclonal antibody c-erb-2
  • monoclonal antibody HER2
  • rhuMAb HER2
• Procedure: magnetic resonance imaging
  Optional correlative studies
  Other Names:

  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
• Procedure: therapeutic conventional surgery
  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

• Experimental: Arm I (HER-2 positive)
  Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, carboplatin IV over 60 minutes, and trastuzumab IV over 90 minutes , then weekly over 30-60 minutes. Treatment repeats every week for 12 weeks in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery.
  Interventions:

  • Drug: Carboplatin
  • Drug: paclitaxel albumin-stabilized nanoparticle formulation
  • Drug: trastuzumab
  • Procedure: magnetic resonance imaging
  • Procedure: therapeutic conventional surgery
• Experimental: Arm II (HER-2 negative)
  Patients receive paclitaxel albumin-stabilized nanoparticle formulation and carboplatin as in Arm I. Patients also receive bevacizumab IV over 90 or 60 or 30 minutes once every two weeks for 5 doses in the absence of disease progression or unacceptable toxicity. In both arms, beginning 21-40 days later, patients undergo surgery.
  Interventions:

  • Drug: Carboplatin
  • Drug: paclitaxel albumin-stabilized nanoparticle formulation
  • Drug: bevacizumab
  • Procedure: magnetic resonance imaging
  • Procedure: therapeutic conventional surgery

• Patients must be women with a histologically confirmed diagnosis of breast cancer that is more than 1 cm and or lymph node positive
• Physical examination, and scans needed for tumor assessment must be performed within 90 days prior to registration
• Patients with the clinical diagnosis of congestive heart failure or angina pectoris are NOT eligible
• Serum creatinine within normal limits within 90 days prior to registration
• Bilirubin within normal limits within 90 days prior to registration
• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 2 x the institutional upper limit of normal within 90 days prior to registration
• Absolute neutrophil count (ANC) of >= 1,500/microliters within 90 days prior to registration
• Platelet count of >= 100,000/microliters within 90 days prior to registration
• Patients must have a performance status of 0-2 by Zubrod criteria
• Pregnant or nursing women may not participate; women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; pregnancy test required for women of childbearing potential
• In calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday four weeks later would be considered day 28; this allows for efficient patient scheduling without exceeding the guidelines; if day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• National Institutes of Health (NIH)
• National Cancer Institute (NCI)