Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery
Condition: Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: doxorubicin hydrochloride; cyclophosphamide; paclitaxel; filgrastim; capecitabine; methotrexate; vinorelbine tartrate; needle biopsy; therapeutic conventional surgery; immunohistochemistry staining method; trastuzumab; tamoxifen citrate; letrozole; laboratory biomarker analysis
Intervention description: Given IV; Given PO; Given IV; Given SC; Given PO; Given IV; Given IV; Correlative studies; Undergo definitive breast surgery; Correlative studies; Given IV; Given PO; Given PO; Correlative studies
Intervention MeSH terms: Tamoxifen; Vinorelbine; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Capecitabine; Methotrexate; Trastuzumab; Letrozole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving combination chemotherapy and filgrastim together
      before surgery works in treating patients with human epidermal growth receptor 2
      (HER2)-positive breast cancer that can be removed by surgery. Drugs used in chemotherapy,
      such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving combination chemotherapy before surgery may make the tumor smaller and
      reduce the amount of normal tissue that needs to be removed. Colony-stimulating factors, such
      as filgrastim, may increase the number of immune cells found in bone marrow or peripheral
      blood and may help the immune system recover from the side effects of chemotherapy. Giving
      doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel
      before surgery may be an effective treatment for breast cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have known tumor HER-2/neu expression; if determination is "intermediate" by
             immunohistochemistry, fluorescent in situ hybridization (FISH) must be performed;
             protocol therapy is determined by HER-2/neu result

          -  Have histologically confirmed, operable breast cancer that is either:

          -  Hormone receptor (estrogen receptor [ER] or progesterone receptor [PR]) positive and
             HER2/neu positive or

          -  ER/PR negative

          -  Have radiographically measurable breast cancer > 1cm (Operable lesions are T1c-T3 and
             N0-N2a; histologic confirmation should be by core needle biopsy only)

          -  Be chemotherapy naïve

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Absolute neutrophil count (ANC) >= 1,500

          -  Platelet count >= 100,000

          -  Serum creatinine =< 1.5 x international upper limit of normal (IULN)

          -  Bilirubin < 2.0

          -  Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvate transaminase
             (SGPT) =< 2 x IULN

          -  Alkaline phosphatase =< 2 x IULN

          -  Have staging studies and tumor assessment prior to registration; staging studies
             include physical exam with bidimensional tumor measurements and mammography,
             ultrasound, or magnetic resonance imaging (MRI) to assess tumor volume; sentinel lymph
             node dissection or axillary needle biopsy must be completed prior to enrollment; MRI
             and positron emission tomography (PET) (fluorodeoxyglucose [FDG],
             methoxyisobutylisonitrile [MIBI] and fluoroestradiol [FES]) imaging will be done
             before enrollment if clinically indicated to assess tumor volume or may be done within
             the first month of study participation on another institutional protocol

          -  Patients with clinically apparent cardiac disease, or history of same, are not
             eligible; patients who are >= 60 years of age or who have a history of hypertension
             must have an echocardiogram or multi gated acquisition scan (MUGA) prior to
             enrollment; patients with breast cancer that is HER-2/neu positive who will receive
             herceptin (trastuzumab) must have an echocardiogram or MUGA scan; the left ventricular
             ejection fraction (LVEF) must be within the institutional normal range; if LVEF is >
             75%, the investigator should consider having the LVEF reviewed or repeating the MUGA
             prior to registration

          -  Women of childbearing potential must have a negative pregnancy test within seven days
             prior to registration

          -  Be informed of the investigational nature of this study and provide written informed
             consent in accordance with institutional and federal guidelines prior to study
             specific screening procedures

        Exclusion Criteria:

          -  Primary tumor =< 1 cm, not measurable; inflammatory disease

          -  Pregnant or lactating; woman of childbearing potential with either a positive or no
             pregnancy test at baseline are excluded; postmenopausal woman must have been
             amenorrheic for at least 12 months to be considered of non-childbearing potential;
             patients must agree to continue contraception for 30 days from the date of the last
             study drug administration; woman of childbearing potential not using a reliable and
             appropriate contraceptive method are excluded

          -  Evidence of distant metastatic disease

          -  Prior chemotherapy or hormonal therapy for breast cancer

          -  Except for the following no other malignancy is allowed: synchronous ipsilateral
             breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or
             squamous cell skin cancer, in situ cervical cancer or other stage I or II cancer from
             which the patient has been disease free for at least 5 years

          -  Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity
             to 5-fluorouracil

          -  Previous enrollment in an investigational drug study within the past four weeks

          -  History of uncontrolled seizures, central nervous system disorders, or psychiatric
             disability judged by the investigator to be clinically significant, precluding
             informed consent, or interfering with compliance with oral drug intake

          -  Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or
             Herceptin are not eligible

          -  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 electrocardiogram (EKG)

          -  Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic > 200 mm/hg)

          -  Current use of digitalis or beta blockers for congestive heart failure (CHF)

          -  Clinically significant pericardial effusion

          -  History of cardiac disease:

          -  Myocardial infarction documented as a clinical diagnosis or by EKG or any other test

          -  Documented congestive heart failure

          -  Documented cardiomyopathy

          -  Documented arrhythmia or cardiac valvular disease that requires medication or is
             medically significant

          -  Major surgery within 4 weeks of the start of study treatment without complete recovery

          -  Lack of physical integrity of the upper gastrointestinal tract or malabsorption
             syndrome

          -  Known, existing uncontrolled coagulopathy

          -  Unwillingness to give written informed consent

          -  Unwillingness to participate or inability to comply with the protocol for the duration
             of the study