A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of Docetaxel Plus Cyclophosphamide or Four Cycles of Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women With Node- Positive or High-Risk Node-Negative HER2-Low Invasive Breast Cancer
This randomized phase III clinical trial studies chemotherapy with or without trastuzumab after surgery to see how well they work in treating women with invasive breast cancer. 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. Giving more than one drug (combination chemotherapy) and giving chemotherapy after surgery may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether combination chemotherapy is more effective with trastuzumab in treating breast cancer.
PRIMARY OBJECTIVES:
I. To determine whether the addition of trastuzumab to chemotherapy (TC or AC?WP) improves invasive disease-free survival (IDFS) in women with resected node-positive or high-risk node-negative breast cancer which is reported as human epidermal growth factor receptor (HER)2-low by all HER2 testing performed.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
NOTE: *Chemotherapy regimen is based on the investigator's preference.
ARM I:
GROUP IA: Patients receive docetaxel intravenously (IV) over 60 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity.
GROUP IB: Patients receive doxorubicin hydrochloride IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-3 weeks after last dose of doxorubicin hydrochloride and cyclophosphamide, patients also receive paclitaxel IV over 60 minutes once weekly for 12 doses in the absence of disease progression or unacceptable toxicity.
ARM II:
GROUP IIA: Patients receive docetaxel and cyclophosphamide as in Group IA. Patients also receive trastuzumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity.
GROUP IIB: Patients receive doxorubicin hydrochloride, cyclophosphamide, and paclitaxel as in Group IB. Patients also receive trastuzumab IV over 30-90 minutes weekly for 12 doses and then every 3 weeks for subsequent doses. Treatment repeats every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 5 years and then every 12 months for 5 years.
- Patients should have a life expectancy of at least 10 years, excluding their diagnosis of breast cancer
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- (comorbid conditions should be taken into consideration, but not the diagnosis of breast cancer)
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Women of reproductive potential must agree to use an effective non-hormonal method of contraception (for example condoms, some intrauterine devices, diaphragms, tubal ligation, vasectomized partner, or abstinence) during therapy and for at least 6 months after the last dose of study therapy (chemotherapy or trastuzumab)
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Submission of tumor samples from the breast surgery is required for all patients
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The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
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Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1
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The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination
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- Synchronous or previous contralateral invasive breast cancer (patients with synchronous and/or previous contralateral DCIS or lobular carcinoma in situ [LCIS] are eligible)
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Previous ipsilateral invasive breast cancer or ipsilateral DCIS (patients with synchronous or previous ipsilateral LCIS are eligible)
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History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization
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Previous therapy with anthracyclines, taxanes, or trastuzumab for any malignancy
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Chemotherapy or HER2-targeted therapy administered for the currently diagnosed breast cancer prior to randomization
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Whole-breast radiation therapy (RT) prior to randomization or partial-breast RT that cannot be completed on or before the date of randomization
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Antibiotics, Antineoplastic
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Antineoplastic Agents, Alkylating
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Antineoplastic Agents, Phytogenic
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Molecular Mechanisms of Pharmacological Action
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Physiological Effects of Drugs
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