Combination Chemotherapy, Surgery, and Radiation Therapy With or Without Dexrazoxane and Trastuzumab in Treating Women With Stage III or Stage IV Breast Cancer
NCT ID: NCT00016276
Last Updated: 2013-01-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE3
396 participants
INTERVENTIONAL
2001-05-31
Brief Summary
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Detailed Description
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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.
V. Determine whether addition of dexrazoxane to doxorubicin and cyclophosphamide reduces the rate of cardiotoxicity in these patients.
VI. Determine whether long-term trastuzumab after local therapy improves disease-free survival in these patients.
VII. Determine whether long-term trastuzumab after local therapy increases the rate of cardiotoxicity in these patients.
VIII. Determine the occurrence of any grade 3 or higher toxicity, second malignancies, acute myelogenous leukemia, or myelodysplastic syndrome in patients treated with these regimens.
IX. Determine the eventual rate of breast conservation in those patients considered candidates for breast conservation prior to neoadjuvant treatment.
X. Determine the clinical response after doxorubicin and cyclophosphamide with or without dexrazoxane and the clinical/mammographic/ultrasound response after paclitaxel with or without trastuzumab, compared to the pathologic response at definitive surgery in these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to stage (inflammatory vs noninflammatory inoperable stage III/ regional stage IV vs operable stage III). Patients are randomized to 1 of 8 treatment arms.
Arm I: 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).
Arm II: 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.
Arm III: 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.
Arm IV: 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.
Arm V: 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.
Arm VI: 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.
Arm VII: 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.
Arm VIII: 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.
Treatment continues in all arms in the absence of distant disease progression. Beginning within 12 weeks of completion of neoadjuvant chemotherapy, hormone receptor-positive patients may receive oral tamoxifen daily for 5 years.
Patients are followed every 6 months for 5 years and then annually for 5 years.
PROJECTED ACCRUAL: A total of 396 patients will be accrued for this study within 4 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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).
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
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.
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
Interventions
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dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
cyclophosphamide
Given IV
paclitaxel
Given IV
trastuzumab
Given IV
therapeutic conventional surgery
Undergo breast conservation surgery, modified radical mastectomy, or mastectomy
radiation therapy
Undergo radiation therapy
tamoxifen citrate
Given orally
laboratory biomarker analysis
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
18 Years
FEMALE
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Mark Graham
Role: PRINCIPAL_INVESTIGATOR
Cancer and Leukemia Group B
Locations
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Cancer and Leukemia Group B
Chicago, Illinois, United States
Countries
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Other Identifiers
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CLB-49808
Identifier Type: -
Identifier Source: secondary_id
CDR0000068617
Identifier Type: REGISTRY
Identifier Source: secondary_id
NCI-2012-02380
Identifier Type: -
Identifier Source: org_study_id
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