Combination Chemotherapy, Surgery, and Radiation Therapy With or Without Dexrazoxane and Trastuzumab in Treating Women With Stage III or Stage IV Breast Cancer
Cardiac Toxicity, Inflammatory Breast Cancer, Stage IIIA Breast Cancer
About this trial
This is an interventional treatment trial for Cardiac Toxicity
Eligibility Criteria
Inclusion Criteria: Histologically confirmed primary infiltrating adenocarcinoma of the breast Confirmed by core needle biopsy or incisional biopsy Amplification of HER-2 by FISH Overexpression (3+) of HER-2 by immunohistochemistry Staging criteria after complete clinical and radiographic staging: T3, N1, M0 Any T, N2 or N3, M0 T4, any N, M0, including clinical or pathological inflammatory disease Regional stage IV disease with supraclavicular or infraclavicular lymph nodes as only site of metastasis Measurable or evaluable disease Prior ductal carcinoma in situ of the ipsilateral breast allowed if treated with excision only without mastectomy or radiation Metaplastic carcinoma allowed Synchronous bilateral primary disease allowed (provided at least 1 cancer meets staging criteria) No dermal lymphatic involvement with clinical inflammatory changes Hormone receptor status: Estrogen receptor positive or negative Progesterone receptor positive or negative Female Granulocyte count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than upper limit of normal (ULN) AST no greater than 2 times ULN Creatinine no greater than 1.5 times ULN LVEF normal by MUGA No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction within the past 6 months, congestive heart failure treated with medications, or uncontrolled hypertension) No other currently active malignancy except nonmelanoma skin cancer Not pregnant or nursing Fertile patients must use effective contraception Patients taking tamoxifen must use effective nonhormonal contraception during and for 2 months after study No prior chemotherapy No other concurrent chemotherapy No more than 4 weeks of prior tamoxifen for disease Prior tamoxifen or raloxifene for longer than 4 weeks as chemoprevention allowed No concurrent tamoxifen or raloxifene No other concurrent hormonal therapy except for steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic See Disease Characteristics No prior radiotherapy for index malignancy No prior radiotherapy to the ipsilateral breast, regional nodes, mediastinum, or heart Prior radiotherapy to the contralateral breast for ductal carcinoma in situ or early stage invasive breast cancer allowed provided earlier radiotherapy does not preclude optimal delivery of study radiotherapy and criterion of low risk for metastasis from first malignancy is met See Disease Characteristics No prior sentinel lymph node biopsy
Sites / Locations
- Cancer and Leukemia Group B
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm I (chemoprotection, monoclonal antibody, radiotherapy)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
Arm IV (chemoprotection, paclitaxel, surgery, radiotherapy)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
Patients receive dexrazoxane IV over 10-20 minutes, doxorubicin IV over 5-10 minutes, and cyclophosphamide IV over 30 minutes on days 1, 22, 43, and 64. Patients receive paclitaxel IV over 1 hour and trastuzumab (Herceptin) IV over 30-90 minutes on days 85, 92, 99, 106, 113, 120, 127, 134, 141, 148, 155, and 162. Approximately 1-2 weeks after completion of neoadjuvant chemotherapy, patients undergo breast conservation surgery, modified radical mastectomy, or mastectomy. Patients with unacceptable toxicity or locoregional disease progression may undergo surgery prior to week 24 (i.e., completion of neoadjuvant chemotherapy). Beginning 2-4 weeks after breast conservation surgery or 3-5 weeks after mastectomy, patients undergo radiotherapy daily 5 days a week for 6-8 weeks. Patients receive long-term trastuzumab IV over 30-90 minutes weekly for 40 weeks beginning on week 36 (day 254).
Patients receive dexrazoxane, doxorubicin, and cyclophosphamide as in arm I. Patients receive paclitaxel (without trastuzumab) as in arm I. Patients undergo surgery and radiotherapy as in arm I. Patients receive long-term trastuzumab as in arm I.
Patients receive dexrazoxane, doxorubicin, and cyclophosphamide as in arm I. Patients receive paclitaxel and trastuzumab as in arm I. Patients undergo surgery and radiotherapy as in arm I. Patients undergo observation only for 40 weeks after completion of radiotherapy.
Patients receive dexrazoxane, doxorubicin, and cyclophosphamide as in arm I. Patients receive paclitaxel as in arm II. Patients undergo surgery and radiotherapy as in arm I. Patients undergo observation as in arm III.
Patients receive doxorubicin and cyclophosphamide (without dexrazoxane) as in arm I. Patients receive paclitaxel and trastuzumab as in arm I. Patients undergo surgery and radiotherapy as in arm I. Patients receive long-term trastuzumab as in arm I.
Patients receive doxorubicin and cyclophosphamide as in arm V. Patients receive paclitaxel as in arm II. Patients undergo surgery and radiotherapy as in arm I. Patients receive long-term trastuzumab as in arm I.
Patients receive doxorubicin and cyclophosphamide as in arm V. Patients receive paclitaxel and trastuzumab as in arm I. Patients undergo surgery and radiotherapy as in arm I. Patients undergo observation as in arm III.
Patients receive doxorubicin and cyclophosphamide as in arm V. Patients receive paclitaxel as in arm II. Patients undergo surgery and radiotherapy as in arm I. Patients undergo observation as in arm III.