Phase II Study With Abraxane, Bevacizumab and Carboplatin in Triple Negative Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Abraxane; Bevacizumab; Carboplatin
Intervention description: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death..; 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death.; area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Breast Cancer; Advanced Breast Cancer; Hormone Receptor AND Her2/neu Negative; Triple Negative; Triple Negative Breast Cancer; Stage IV or Inoperable Stage III Breast Cancer

Summary:

      Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane®
      (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and
      tolerability. When combined with a taxane, platinum agents improve response in metastatic
      breast cancer, with carboplatin conferring less toxicity than cisplatin. Monoclonal
      antibodies including bevacizumab target vascular endothelial growth factor (VEGF) to reduce
      angiogenesis. We hypothesize that the previously-untested combination of weekly Abraxane® and
      carboplatin plus biweekly bevacizumab will lengthen time to progression without producing
      intolerable toxicity.
    

Eligibility criteria:

        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 < 150 and/or
             diastolic 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.