Phase 2 Trial of Pertuzumab and Trastuzumab With Weekly Paclitaxel and Chemotherapy for HER2 Positive Breast Cancer
Condition: Her2-Positive Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pertuzumab; Trastuzumab; Paclitaxel; 5-fluorouracil; Epirubicin; Cyclophosphamide
Intervention description: First dose is 840mg, maintenance dose is 420mg. Pertuzumab will be administered once every 3 weeks for 24 weeks (8 doses total); For weeks 1-12, first dose is 4 mg/kg, maintenance dose is 2 mg/kg administered every week (12 doses total).
For weeks 13-24, dose is 6mg/kg administered every 3 weeks (4 doses total).; Administered at 80mg/m2 every week from week 1 to 12 (12 doses total).; Administered at 500 mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).; Administered at 75mg/m2 every 3 weeks during weeks 13-24 (4 doses total).; Administered at 500mg/m2 for every 3 weeks during weeks 13-24 (4 doses total).
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Fluorouracil; Trastuzumab; Epirubicin; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The main goal of this clinical trial is to test if adding pertuzumab (Perjeta), improves the
      anticancer activity of the combination chemotherapy regimen of trastuzumab (Herceptin)
      concomitant with paclitaxel, 5-fluorouracil, epirubicin, and cyclophosphamide (T-FEC). The
      study will also test the safety of this therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        - Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer
        for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment
        following NCCN practice guidelines.

        HER2 overexpression or amplification will be based on local test results and is defined as
        either:

        (i) IHC staining of 3+ (uniform, intense membrane staining) in greater than or equal to 10%
        of invasive tumor cells or, (ii) Fluorescent in situ hybridization (FISH) result of more
        than six HER2 gene copies per nucleus or, (iii) FISH ratio (HER2 gene signals to chromosome
        17 signals) of greater than or equal to 2.0.

          -  Patients with synchronous bilateral breast cancers are eligible if at least one of the
             tumors is HER2-positive.

          -  Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as
             determined by either ECHO or MUGA, or within the institution's normal limits.

          -  Women of childbearing potential must have a negative pregnancy test (serum or urine
             beta HCG) prior to initiation of chemotherapy. Both female and male breast cancer
             patients who are sexually active have to agree to practice contraception while
             participating in the trial and for 3 month after completion of therapy.

          -  Adequate bone marrow function as indicated by the following:

          -  ANC greater than or equal to 1500/uL

          -  Platelets greater than or equal to 100,000/uL

          -  Hemoglobin greater than or equal to 10 g/dL

          -  Adequate renal function, as indicated by creatinine less than or equal to 1.5 times
             upper limit of normal (ULN)

          -  Adequate liver function, as indicated by bilirubin less than or equal to 1.5 X ULN and
             AST or ALT less than or equal to 2x ULN.

          -  Signed informed consent.

        Exclusion Criteria:

        Patients will be excluded from the study based on any of the following criteria:

          -  Patients who underwent partial excisional biopsy, lumpectomy, segmental mastectomy,
             modified radical mastectomy or sentinel node biopsy and, therefore cannot be assessed
             for pathologic response accurately.

          -  Patients who are high risk for developing the following anthracycline, paclitaxel,
             trastuzumab or pertuzumab related toxicities including:

        History of congestive heart failure, myocardial infarction or cardiomyopathy, uncontrolled
        hypertension despite adequate medications Pre-existing peripheral neuropathy > grade 3
        Prior anthracycline therapy Known hypersensitivity to any of the study medications Patients
        older than age 65 due to increased risk of cardiotoxicity

          -  Active infection requiring systemic antibiotic therapy.

          -  Pregnant or lactating women