Combination Chemotherapy and Paclitaxel Plus Trastuzumab in Treating Women With Palpable Breast Cancer That Can Be Removed by Surgery
Condition: HER2/Neu Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Cyclophosphamide; Epirubicin Hydrochloride; Laboratory Biomarker Analysis; Paclitaxel; Therapeutic Conventional Surgery; Trastuzumab
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Undergo surgery; Given IV
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Trastuzumab; Albumin-Bound Paclitaxel; Epirubicin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 280.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying giving fluorouracil together with epirubicin and
      cyclophosphamide followed by paclitaxel and trastuzumab to see how well it works compared
      with giving paclitaxel together with trastuzumab followed by fluorouracil, epirubicin,
      cyclophosphamide, and trastuzumab in treating women with palpable breast cancer that can be
      removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal
      antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the
      ability of tumor cells to grow and spread. Others find tumor cells and help kill them or
      carry tumor-killing substances to them. It is not yet known whether it is more effective to
      give combination chemotherapy before or after treatment with paclitaxel plus trastuzumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of invasive adenocarcinoma by core needle biopsy

               -  Fine needle aspiration allowed provided primary tumor size < 2 cm and lymph node
                  metastases are present

               -  Excisional biopsy of the primary tumor allowed provided biopsy-positive lymph
                  nodes are present

          -  Primary tumor ≥ 2 cm and/or ≥ 1 biopsy-positive lymph node

          -  HER2-positive disease

               -  Confirmation by fluorescent in situ hybridization (FISH) requires gene
                  amplification

               -  Confirmation by immunohistochemistry (IHC) requires a strongly positive (3+)
                  staining intensity score

          -  Ductal carcinoma in situ (DCIS) or synchronous DCIS of the contralateral breast
             regardless of prior therapy allowed

               -  Synchronous invasive breast cancer not allowed

          -  Ipsilateral DCIS treated by local excision with or without hormonal therapy allowed

               -  Those treated with radiation therapy are not allowed

          -  No definitive clinical or radiologic evidence of metastatic disease

          -  No history of invasive breast cancer

          -  Hormone receptor status known

          -  Menopausal status not specified

          -  ECOG performance status of 0 -1

          -  Absolute neutrophil count ≥ 1,200/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Total bilirubin normal unless the patient has a grade 1 bilirubin elevation (normal to
             1.5 times upper limit of normal [ULN]) resulting from Gilbert disease or similar
             syndrome due to slow conjugation of bilirubin

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  AST ≤ 1.5 times ULN

          -  Creatinine normal

          -  Left ventricular ejection fraction (LVEF) ≥ 55 by multi gated acquisition scan (MUGA)
             or echocardiogram (ECHO) within the past 3 months

          -  Patients with either skeletal pain or alkaline phosphatase that is > ULN but ≤ 2.5
             times ULN allowed if bone scans fail to demonstrate metastatic disease

               -  Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or
                  biopsy

          -  Prior non-breast malignancies allowed if disease-free for 5 years since completion of
             initial treatment regimen and deemed by their physician to be at low risk for
             recurrence

               -  Patients who had the following cancers are eligible if diagnosed and treated
                  within the past 5 years:

                    -  Carcinoma in situ of the cervix

                    -  Colon carcinoma in situ

                    -  Melanoma in situ

                    -  Basal cell and squamous cell carcinoma of the skin

          -  No cardiac disease that would preclude the use of epirubicin hydrochloride or
             trastuzumab (Herceptin®) including any of the following:

               -  Active cardiac disease

               -  Angina pectoris that requires the use of antianginal medication

               -  Cardiac arrhythmia requiring medication

               -  Severe conduction abnormality

               -  Clinically significant valvular disease

               -  Cardiomegaly on chest x-ray

               -  Ventricular hypertrophy on EKG

               -  Patient's with poorly controlled hypertension ( i.e., diastolic greater than 100
                  mm/Hg)

                    -  Patients with hypertension that is well controlled on medication are
                       eligible

               -  History of cardiac disease

               -  Myocardial infarction documented as a clinical diagnosis or by EKG or any other
                  tests

               -  Documented congestive heart failure

               -  Documented cardiomyopathy

          -  No sensory or motor neuropathy ≥ grade 2, as defined by the NCI's CTCAE v3.0

          -  Women of reproductive potential must agree to use an effective non-hormonal method of
             contraception during therapy

          -  Women of child bearing potential must have a negative urine or serum pregnancy test
             within 2 weeks of registration

          -  Not pregnant or nursing

          -  No psychiatric or addictive disorders or other conditions that, in the opinion of the
             investigator, would preclude the patient from meeting the study requirements

          -  No non-malignant systemic disease (e.g., cardiovascular, renal, hepatic) that would
             preclude treatment with either of the treatment regimens

          -  No prior surgical axillary staging procedure

               -  Prior non-excisional biopsy of an axillary node allowed

          -  No prior treatment for this breast cancer

               -  Hormonal therapy allowed if had been given for up to a total of 28 days anytime
                  after diagnosis and before study entry

               -  Hormonal therapy must stop at or before study entry and be re-started, if
                  indicated, following surgery

          -  No prior therapy with anthracyclines or taxanes for any malignancy

          -  No other investigational agents within the past 30 days

          -  No concurrent sex hormonal therapy (e.g., birth control pills, ovarian hormonal
             replacement therapy)

          -  No concurrent therapy with any hormonal agent such as raloxifene, tamoxifen, or other
             selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer
             prevention