A 2X2X2 Factorial Randomized Phase III Trial Of Multimodality Therapy Comparing 4 Cycles Of Doxorubicin And Cyclophosphamide With Or Without Dexrazoxane (AC+/-Z) Followed By 12 Weeks Of Weekly Paclitaxel With Or Without Trastuzumab (T+/-H) Followed By Local Therapy Followed By 40 Weeks Of Weekly Trastuzumab Or None In Women With HER-2+ STAGE IIIA, IIIB OR REGIONAL STAGE IV BREAST CANCER
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 396
- 试验地点
- 1
- 主要终点
- Median number of positive axillary lymph nodes
研究概览
简要总结
Randomized phase III trial to compare the effectiveness of combination chemotherapy, surgery, and radiation therapy with or without dexrazoxane and trastuzumab in treating women who have stage IIIA, stage IIIB or stage IV breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as dexrazoxane, may protect normal cells from the side effects of chemotherapy. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy combined with surgery and radiation therapy is more effective with or without dexrazoxane and trastuzumab in treating breast cancer
详细描述
OBJECTIVES:
I. Determine the time to locoregional recurrence, time to completion of treatment, and overall survival in women with HER-2+ stage IIIA or IIIB or regional stage IV breast cancer treated with doxorubicin and cyclophosphamide with or without dexrazoxane, followed by paclitaxel with or without trastuzumab (Herceptin), followed by surgery and radiotherapy with or without trastuzumab.
II. Determine whether addition of trastuzumab to paclitaxel therapy improves response at 24 weeks of therapy in these patients.
III. Determine whether addition of trastuzumab to paclitaxel therapy increases the rate of cardiotoxicity in these patients.
IV. Determine whether addition of dexrazoxane to doxorubicin and cyclophosphamide compromises response in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- 未提供
研究组 & 干预措施
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: dexrazoxane hydrochloride (Drug)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: doxorubicin hydrochloride (Drug)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: cyclophosphamide (Drug)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: paclitaxel (Drug)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: trastuzumab (Biological)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: therapeutic conventional surgery (Procedure)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: radiation therapy (Radiation)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: tamoxifen citrate (Drug)
Arm I (chemoprotection, monoclonal antibody, 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).
干预措施: laboratory biomarker analysis (Other)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: dexrazoxane hydrochloride (Drug)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: doxorubicin hydrochloride (Drug)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: cyclophosphamide (Drug)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: paclitaxel (Drug)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: trastuzumab (Biological)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: therapeutic conventional surgery (Procedure)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: radiation therapy (Radiation)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: tamoxifen citrate (Drug)
Arm II (chemoprotection, radiotherapy, surgery, trastuzumab)
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.
干预措施: laboratory biomarker analysis (Other)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: dexrazoxane hydrochloride (Drug)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: doxorubicin hydrochloride (Drug)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: cyclophosphamide (Drug)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: paclitaxel (Drug)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: trastuzumab (Biological)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: therapeutic conventional surgery (Procedure)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: radiation therapy (Radiation)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: tamoxifen citrate (Drug)
Arm III (chemoprotection, monoclonal antibody, radiotherapy)
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.
干预措施: laboratory biomarker analysis (Other)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: dexrazoxane hydrochloride (Drug)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: doxorubicin hydrochloride (Drug)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: cyclophosphamide (Drug)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: paclitaxel (Drug)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: therapeutic conventional surgery (Procedure)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: radiation therapy (Radiation)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: tamoxifen citrate (Drug)
Arm IV (chemoprotection, paclitaxel, surgery, 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.
干预措施: laboratory biomarker analysis (Other)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: doxorubicin hydrochloride (Drug)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: cyclophosphamide (Drug)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: paclitaxel (Drug)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: trastuzumab (Biological)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: therapeutic conventional surgery (Procedure)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: radiation therapy (Radiation)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: tamoxifen citrate (Drug)
Arm V (combination chemo, radiotherapy, long term trastuzumab)
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.
干预措施: laboratory biomarker analysis (Other)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: doxorubicin hydrochloride (Drug)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: cyclophosphamide (Drug)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: paclitaxel (Drug)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: trastuzumab (Biological)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: therapeutic conventional surgery (Procedure)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: radiation therapy (Radiation)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: tamoxifen citrate (Drug)
Arm VI (combination chemo, paclitaxel, surgery, radiotherapy)
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.
干预措施: laboratory biomarker analysis (Other)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: doxorubicin hydrochloride (Drug)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: cyclophosphamide (Drug)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: paclitaxel (Drug)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: trastuzumab (Biological)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: therapeutic conventional surgery (Procedure)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: radiation therapy (Radiation)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: tamoxifen citrate (Drug)
Arm VII (combination chemo, monoclonal antibody, radiotherapy)
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.
干预措施: laboratory biomarker analysis (Other)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: doxorubicin hydrochloride (Drug)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: cyclophosphamide (Drug)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: paclitaxel (Drug)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: therapeutic conventional surgery (Procedure)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: radiation therapy (Radiation)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: tamoxifen citrate (Drug)
Arm VIII (combination chemotherapy, paclitaxel, radiotherapy)
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.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Median number of positive axillary lymph nodes
时间窗: At 24 weeks
Compared in the Herceptin and no Herceptin groups and in the dexrazoxane versus no dexrazoxane groups using a chi-square test and a two-sample t test, respectively.
Pathologic complete response (CR) rate in the breast and axilla
时间窗: At 24 weeks
Compared in the Herceptin and no Herceptin groups and in the dexrazoxane versus no dexrazoxane groups using a chi-square test and a two-sample t test, respectively.
Cardiac toxicity, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
时间窗: At 78 weeks
Assessment will use exact binomial comparison of two proportions.
Disease-free survival
时间窗: Date of study entry to date of first relapse (local or distant) or death due to any cause, assessed up to 10 years
Proportional hazards regression models will be used.
次要结局
- Occurrence of grade 3 or higher late cardiac or neurological toxicity, or secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS)(Up to 10 years)
- Clinical/radiographic response in the breast and axilla after doxorubicin hydrochloride and cyclophosphamide with or without dexrazoxane hydrochloride(At 12 weeks)
- Clinical/radiographic response in the breast and axilla after paclitaxel with or without trastuzumab(At 24 weeks)
- Time to local/regional recurrence(Up to 10 years)
- Time to completion of treatment through radiotherapy(Up to 5 years)
- Rate of breast conservation for patients considered "candidates" prior to treatment(Up to 10 years)
- Overall survival(Date of study entry to date of due to any cause, assessed up to 10 years)