Phase II Study With Abraxane, Bevacizumab and Carboplatin in Triple Negative Metastatic Breast Cancer

Inclusion Criteria

• Tissue block containing tumor to confirm metastatic breast cancer is required;
• Measurable disease according to RECIST criteria
• "Triple negative" disease defined as tumor demonstrating no expression for estrogen, progesterone or human epidermal growth factor receptor 2(HER2)receptors. "No expression" is categorized as ≤ 10% of cells staining or Allred ≤ 2;
• Aged 18 years or older;
• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1; life expectancy ≥ 3 months;
• Patients may have received 0 - 1 prior therapies (except taxanes in the metastatic setting). An interval of at least 1 week must have elapsed since prior chemotherapy or hormonal therapy for metastatic disease; at least 6 months must have elapsed since prior adjuvant therapy;
• ≥ 2 weeks between surgery and study enrollment (≥ 4 weeks between major surgery (defined as open abdominal/thoracic/cardiac) and study enrollment;
• Laboratory tests performed within 14 days of study entry:
• Granulocytes ≥ 1,500/µL;
• Platelets ≥ 100,000/µL;
• Hemoglobin ≥ 9 gm/dL;
• Total bilirubin ≤ institutional upper limit of normal (ULN);
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN;
• Alkaline phosphatase ≤ 2.5 times ULN;
• Estimated creatinine clearance ≥ 60 mL/min.
• left ventricular ejection fraction (LVEF)≥ 50% by multigated acquisition (MUGA)/Echocardiogram;
• Informed consent to receive protocol treatment, to provide biologic specimens, and to complete neurotoxicity questionnaires;
• Cognitive and communication skills to comply with study and/or follow-up procedures;
• No reproductive potential:
• If pre-menopausal: Negative serum pregnancy test and patient agreement to use adequate contraceptive method (abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during and for 3 months after completion of treatment.
• If post-menopausal: Amenorrhea for ≥ 12 months.

Exclusion Criteria

• Pregnant or breast feeding;
• Prior treatment with Abraxane®, carboplatin or bevacizumab, or any taxane for metastatic breast cancer;
• Known hypersensitivity to any component of any study drug;
• Active infection;
• Current neuropathy ≥ grade 2;
• central nervous system (CNS) metastases as determined by head CT with contrast;
• History of bleeding within the past 6 months or active bleeding disorder;
• Serious non-healing wound, ulcer or bone fracture;
• Uncontrolled congestive heart failure (CHF), or history of myocardial infarction(MI), unstable angina, stroke, or transient ischemia within previous 6 months;
• Inadequately controlled hypertension (defined as systolic blood pressure 100 mmHg on antihypertensive medications; prior history of hypertensive crisis or hypertensive encephalopathy;
• Proteinuria (defined as urine protein: creatinine (UPC) ratio ≥ 1.0 or urine dipstick ≥ 2+.
• Significant vascular disease (aortic aneurysm, aortic dissection) or symptomatic peripheral vascular disease;
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within previous 6 months;
• Uncontrolled serious contraindicated medical condition or psychiatric illness.