Carboplatin, Abraxane, Avastin as Neoadjuvant Therapy for Her2-Negative Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Abraxane; Carboplatin; Avastin
Intervention description: Abraxane 100 mg/m2 IV over 30 minutes weekly x 12 weeks; Carboplatin at AUC 6 over 30 min IV weeks 1,4,7, and 10; Avastin 15 mg/kg IV over 30-90 minutes weeks 1,4,7, and 10 (in Cohort 2, omit dose of Avastin on week 10)
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

Summary:

      In the MDACC/BrUOG neoadjuvant trial with weekly paclitaxel followed by Fluorouracil Plus
      Doxorubicin and Cyclophosphamide (FAC), the pathologic complete response (pCR) rate in
      HER2(-) patients was 20%. The investigators' goal is to develop an induction chemotherapy
      regimen that will have a pCR rate above 30% in patients with HER2(-) disease. Based on a
      1-sided 95% confidence interval using normal approximation with an expected pCR rate of at
      least 35%, approximately 28 patients are required for each cohort. With an assumed pCR rate
      of at least 35%, the investigators will have approximately 70% statistical power to conclude,
      with 90% certainty, that the pCR rate with the novel regimen exceeds 20%. The study will
      accrue approximately 60 patients in two cohorts with an inevaluable rate that does not exceed
      10%.
    

Eligibility criteria:

        Eligibility criteria

        Inclusion criteria:

          -  Histologically documented adenocarcinoma of the breast

          -  ANC > 1000 cells

          -  Female; age > 18

          -  Zubrod PS 0-1

          -  Platelets > 100,000

          -  Stage IIA-IIIB disease

          -  Total bilirubin < 1.5 ULN

          -  No evidence of any metastatic disease

          -  Serum Creatinine < 1.5 gm/dl

          -  No prior systemic therapy for breast cancer or Creat Cl > 30 ml/min

          -  Not pregnant or lactating

          -  Serum ALT < 2.0 ULN

          -  ER, PR and HER2 status required

          -  LVEF (MUGA/echo WNL)

          -  No baseline > 2 neuropathy

          -  Urine protein: creat ratio < 1.0

          -  HER2-negative - either IHC 0-1+ or FISH ratio < 2.0

          -  Hemoglobin > 9 gm/dl

          -  (FISH testing is required for all HER2 2-3+ tumors by IHC)

        Exclusion criteria:

          -  No Histologically documented adenocarcinoma of the breast

          -  No-ANC > 1000 cells

          -  Female; age < 18

          -  Zubrod PS > 0-1

          -  Platelets < 100,000

          -  Stage IV disease

          -  Total bilirubin > 1.5 ULN

          -  metastatic disease

          -  Serum Creatinine > 1.5 gm/dl

          -  prior systemic therapy for breast cancer or Creat Cl > 30 ml/min

          -  pregnant or lactating

          -  Serum ALT > 2.0 ULN baseline > 2 neuropathy

          -  Urine protein: creat ratio >1.0

          -  HER2-positive

          -  Hemoglobin < 9 gm/dl