Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Positive Breast Cancer
NCT ID: NCT00093795
Last Updated: 2018-01-11
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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Recruitment Status
COMPLETED
Clinical Phase
PHASE3
Total Enrollment
4894 participants
Study Classification
INTERVENTIONAL
Study Start Date
2004-10-31
Study Completion Date
2016-06-30
Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, doxorubicin , cyclophosphamide, paclitaxel, and gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any remaining tumor cells.
PURPOSE: This randomized phase III trial is studying three different combination chemotherapy regimens and comparing how well they work in treating women who have undergone surgery for node-positive breast cancer.
PURPOSE: This randomized phase III trial is studying three different combination chemotherapy regimens and comparing how well they work in treating women who have undergone surgery for node-positive breast cancer.
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Detailed Description
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OBJECTIVES:
Primary
* Compare disease-free survival in women with node-positive breast cancer treated with 3 different adjuvant chemotherapy regimens comprising dose-dense doxorubicin, cyclophosphamide, paclitaxel, and gemcitabine vs docetaxel, doxorubicin, and cyclophosphamide vs dose-dense doxorubicin, cyclophosphamide, and paclitaxel.
Secondary
* Compare overall survival, recurrence-free interval, and distant recurrence-free interval, in patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive lymph nodes (1-3 vs 4-9 vs ≥ 10), hormone receptor status (estrogen receptor \[ER\]- and progesterone receptor \[PgR\]- negative vs ER- and/or PgR-positive), type of prior surgery and planned radiotherapy (lumpectomy and local radiotherapy \[RT\] without regional RT vs lumpectomy and local RT with regional RT vs mastectomy without RT vs mastectomy with local or regional RT). Patients are randomized to 1 of 3 treatment arms.
* Group 1: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses.
* Group 2: Patients receive AC chemotherapy comprising doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 14 days for 4 courses. Beginning 14 days after the last dose of AC, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses.
* Group 3: Patients receive AC chemotherapy as in Group 2. Beginning 14 days after the last dose of AC, patients receive paclitaxel as in Group 2 and gemcitabine IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4 courses.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Beginning 3-12 weeks after the last dose of chemotherapy, patients with ER-positive and/or PgR-positive tumors receive hormonal therapy.
Beginning no sooner than 3 weeks after the last dose of chemotherapy, patients treated with lumpectomy undergo whole-breast radiotherapy. Patients treated with mastectomy may undergo chest wall and/or regional nodal radiotherapy.
Patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 4,800 patients will be accrued for this study within 4 years.
Primary
* Compare disease-free survival in women with node-positive breast cancer treated with 3 different adjuvant chemotherapy regimens comprising dose-dense doxorubicin, cyclophosphamide, paclitaxel, and gemcitabine vs docetaxel, doxorubicin, and cyclophosphamide vs dose-dense doxorubicin, cyclophosphamide, and paclitaxel.
Secondary
* Compare overall survival, recurrence-free interval, and distant recurrence-free interval, in patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive lymph nodes (1-3 vs 4-9 vs ≥ 10), hormone receptor status (estrogen receptor \[ER\]- and progesterone receptor \[PgR\]- negative vs ER- and/or PgR-positive), type of prior surgery and planned radiotherapy (lumpectomy and local radiotherapy \[RT\] without regional RT vs lumpectomy and local RT with regional RT vs mastectomy without RT vs mastectomy with local or regional RT). Patients are randomized to 1 of 3 treatment arms.
* Group 1: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses.
* Group 2: Patients receive AC chemotherapy comprising doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 14 days for 4 courses. Beginning 14 days after the last dose of AC, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses.
* Group 3: Patients receive AC chemotherapy as in Group 2. Beginning 14 days after the last dose of AC, patients receive paclitaxel as in Group 2 and gemcitabine IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4 courses.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Beginning 3-12 weeks after the last dose of chemotherapy, patients with ER-positive and/or PgR-positive tumors receive hormonal therapy.
Beginning no sooner than 3 weeks after the last dose of chemotherapy, patients treated with lumpectomy undergo whole-breast radiotherapy. Patients treated with mastectomy may undergo chest wall and/or regional nodal radiotherapy.
Patients are followed every 6 months for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 4,800 patients will be accrued for this study within 4 years.
Conditions
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Breast Cancer
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Group 1: TAC X 6
Doxorubicin, cyclophosphamide, and docetaxel.
Group Type
ACTIVE_COMPARATOR
Cyclophosphamide
Intervention Type
DRUG
Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles
Docetaxel
Intervention Type
DRUG
75 mg/m2 IV every 21 days for 6 cycles
Doxorubicin
Intervention Type
DRUG
Group 1: 50 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles
Group 2: AC X 4 then P X 4
Doxorubicin, cyclophosphamide, and paclitaxel
Group Type
ACTIVE_COMPARATOR
Cyclophosphamide
Intervention Type
DRUG
Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles
Paclitaxel
Intervention Type
DRUG
175 mg/m2 IV every 14 days for 4 cycles
Doxorubicin
Intervention Type
DRUG
Group 1: 50 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles
Group 3: AC X 4 then PG X 4
Doxorubicin, cyclophosphamide, paclitaxel and gemcitabine
Group Type
EXPERIMENTAL
Cyclophosphamide
Intervention Type
DRUG
Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles
Gemcitabine
Intervention Type
DRUG
2000 mg/m2 IV every 14 days for 4 cycles
Paclitaxel
Intervention Type
DRUG
175 mg/m2 IV every 14 days for 4 cycles
Doxorubicin
Intervention Type
DRUG
Group 1: 50 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles
Interventions
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Cyclophosphamide
Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles
Intervention Type
DRUG
Docetaxel
75 mg/m2 IV every 21 days for 6 cycles
Intervention Type
DRUG
Gemcitabine
2000 mg/m2 IV every 14 days for 4 cycles
Intervention Type
DRUG
Paclitaxel
175 mg/m2 IV every 14 days for 4 cycles
Intervention Type
DRUG
Doxorubicin
Group 1: 50 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles
Intervention Type
DRUG
Other Intervention Names
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C
Taxotere
T
Gemzar
G
Taxol
P
A
Adriamycin
Eligibility Criteria
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Inclusion Criteria
* The patient must consent to participate in the study and must have signed an approved consent form conforming with federal and institutional guidelines.
* The patient must have a life expectancy of at least 10 years and a Zubrod performance status of 0 or 1. (Comorbid conditions but not the diagnosis of breast cancer should be taken into consideration when determining life expectancy.)
* The interval between the last surgery for breast cancer staging or treatment and randomization must be no more than 84 days.
* The tumor must be invasive carcinoma of the breast on histologic examination.
* All of the following staging criteria must be met:
* By clinical and pathologic evaluation, primary tumor must be T1-3;
* By clinical evaluation, ipsilateral nodes must be cN0, cN1, or cN2a;
* By pathologic evaluation, ipsilateral nodes must be pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b (only if due to microscopic involvement of internal mammary node detected by sentinel lymph node dissection and with more than 3 positive axillary lymph nodes).
* Patients must have an estrogen receptor (ER) analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then progesterone receptor (PgR) analysis must be performed. If ER analysis is positive, PgR analysis is desired, but not mandatory. ("Marginal" or "borderline" results \[i.e., those not definitely negative\] will be considered positive regardless of the methodology used.)
* Patients must have had either a lumpectomy or a total mastectomy. Patients must have completed one of the following procedures for evaluation of pathologic nodal status.
* Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes (This approach is strongly recommended.)
* Sentinel lymphadenectomy alone if one of the following criteria is met:
* Pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1b
* Surgeon elects not to remove additional non-sentinel nodes (This approach is strongly discouraged, but will not preclude participation in B-38.)
* Axillary lymphadenectomy without sentinel node isolation procedure.
* Patients must have no clinical or radiologic evidence of metastatic disease.
* Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN are eligible for inclusion in the study if bone scans fail to demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
* Patients with aspartate transaminase (AST) or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging fails to demonstrate metastatic disease and the following requirements are met at the time of randomization.
* Postoperative absolute granulocyte count (AGC) must be greater than or equal to 1200/mm3.
* Postoperative platelet count must be greater than or equal to 100,000/mm3.
* The following criteria for postoperative evidence of adequate hepatic function must be met:
* total bilirubin must be less than or equal to ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
* alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and
* the AST must be less than or equal to 1.5 x ULN for the lab; and
* alkaline phosphatase and AST cannot both be greater than ULN.
* Postoperative serum creatinine must be less than or equal to ULN.
* At the time of randomization, the patient must have had the following: history and physical exam, EKG, and imaging of the chest within the past 3 months and bilateral mammogram within the past 6 months.
* Within 3 months prior to entry, the patient must have a baseline left ventricular ejection fraction (LVEF), measured by Multiple Gated Acquisition (MUGA) scan or echocardiogram, greater than or equal to lower limit of normal (LLN) for the facility performing the procedure and no evidence of regional wall abnormalities.
* Patients with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior to randomization and are deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
* Special conditions for eligibility of lumpectomy patients: radiation therapy and surgery. Patients treated by lumpectomy must meet all the eligibility criteria in addition to the following:
* Generally, lumpectomy should be reserved for tumors less than 5 cm. However, at the investigator's discretion, patients treated with lumpectomy for tumors greater than or equal to 5 cm are eligible if eligibility criteria for lumpectomy are met.
* The margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. In patients for whom pathologic examination demonstrates tumor present at the line of resection, additional operative procedures may be performed to obtain clear margins. This is permissible even if axillary evaluation has been completed. Patients in whom tumor is still present at the resected margin after re-excision(s) must undergo total mastectomy to be eligible. (Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.)
* Irradiation of regional lymph nodes is optional, but plans for radiation therapy must be declared by the investigator prior to randomization for stratification purposes.
* Special conditions for eligibility of mastectomy patients: radiation therapy o Postmastectomy chest wall and/or regional nodal irradiation is optional. Plans for radiation in mastectomy patients must be declared by the investigator prior to randomization for stratification purposes.
Ineligibility Criteria
* Male patients are not eligible for this study. Women with one or more of the following conditions or prior therapies are also ineligible for this study:
* Tumor that has been determined to be human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
* Contralateral breast cancer (invasive or DCIS) or a mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant.
* Primary tumor staged as T4 for any reason.
* Clinical nodal stages including cN2b and cN3 or pathologic nodal stages including pN0(i+), pN2b, pN3b with clinically apparent internal mammary nodes, or pN3c.
* Suspicious nodes in the contralateral axilla or suspicious supraclavicular nodes. Patients with these conditions are considered ineligible unless there is biopsy evidence that these are not involved with tumor.
* Prior history of breast cancer, including DCIS (patients with a history of LCIS are eligible).
* Treatment, including radiation therapy, chemotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to randomization. One exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry. In such a case, hormonal therapy must stop at or before randomization and be re-started, if indicated, following chemotherapy. A second exception is radiation therapy for patients enrolled in NSABP B-39 and assigned to partial breast irradiation (Group 2). These patients may have received RT prior to B-38 study entry.
* Prior therapy with anthracyclines or taxanes for any malignancy.
* Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
* Therapy with any hormonal agents such as raloxifene (Evista®), tamoxifen, or other selective estrogen-receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.
* Cardiac disease that would preclude the use of anthracyclines. This includes:
* history of myocardial infarction documented by elevated cardiac enzymes or regional wall abnormalities on assessment of left ventricular (LV) function;
* angina pectoris that requires the use of anti-anginal medication;
* any history of documented congestive heart failure;
* serious cardiac arrhythmia requiring medication;
* severe conduction abnormality;
* valvular disease with documented cardiac function compromise; and
* uncontrolled hypertension defined as blood pressure greater than 160/100 on antihypertensive therapy.
* Conditions that would prohibit administration of corticosteroids.
* Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0.
* Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from receiving any of the treatment options or would prevent prolonged follow-up.
* History of hepatitis B or C.
* Pregnancy or lactation at the time of proposed randomization. Women of reproductive potential must agree to use an effective non-hormonal method of contraception.
* Concurrent treatment with other investigational agents for the treatment of breast cancer.
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
* Special conditions for ineligibility of lumpectomy patients: radiation therapy and surgery
* For patients treated by lumpectomy, whole breast irradiation is required.
* The following patients will be ineligible:
* Patients with diffuse tumors (as demonstrated on mammography) treated with lumpectomy. (These patients are eligible if they undergo mastectomy.)
* Patients treated with lumpectomy in whom there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant. Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins.
* Patients in whom the margins of the resected specimen are involved with invasive tumor or DCIS.
* The patient must have a life expectancy of at least 10 years and a Zubrod performance status of 0 or 1. (Comorbid conditions but not the diagnosis of breast cancer should be taken into consideration when determining life expectancy.)
* The interval between the last surgery for breast cancer staging or treatment and randomization must be no more than 84 days.
* The tumor must be invasive carcinoma of the breast on histologic examination.
* All of the following staging criteria must be met:
* By clinical and pathologic evaluation, primary tumor must be T1-3;
* By clinical evaluation, ipsilateral nodes must be cN0, cN1, or cN2a;
* By pathologic evaluation, ipsilateral nodes must be pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b (only if due to microscopic involvement of internal mammary node detected by sentinel lymph node dissection and with more than 3 positive axillary lymph nodes).
* Patients must have an estrogen receptor (ER) analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then progesterone receptor (PgR) analysis must be performed. If ER analysis is positive, PgR analysis is desired, but not mandatory. ("Marginal" or "borderline" results \[i.e., those not definitely negative\] will be considered positive regardless of the methodology used.)
* Patients must have had either a lumpectomy or a total mastectomy. Patients must have completed one of the following procedures for evaluation of pathologic nodal status.
* Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes (This approach is strongly recommended.)
* Sentinel lymphadenectomy alone if one of the following criteria is met:
* Pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1b
* Surgeon elects not to remove additional non-sentinel nodes (This approach is strongly discouraged, but will not preclude participation in B-38.)
* Axillary lymphadenectomy without sentinel node isolation procedure.
* Patients must have no clinical or radiologic evidence of metastatic disease.
* Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN are eligible for inclusion in the study if bone scans fail to demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
* Patients with aspartate transaminase (AST) or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging fails to demonstrate metastatic disease and the following requirements are met at the time of randomization.
* Postoperative absolute granulocyte count (AGC) must be greater than or equal to 1200/mm3.
* Postoperative platelet count must be greater than or equal to 100,000/mm3.
* The following criteria for postoperative evidence of adequate hepatic function must be met:
* total bilirubin must be less than or equal to ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
* alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and
* the AST must be less than or equal to 1.5 x ULN for the lab; and
* alkaline phosphatase and AST cannot both be greater than ULN.
* Postoperative serum creatinine must be less than or equal to ULN.
* At the time of randomization, the patient must have had the following: history and physical exam, EKG, and imaging of the chest within the past 3 months and bilateral mammogram within the past 6 months.
* Within 3 months prior to entry, the patient must have a baseline left ventricular ejection fraction (LVEF), measured by Multiple Gated Acquisition (MUGA) scan or echocardiogram, greater than or equal to lower limit of normal (LLN) for the facility performing the procedure and no evidence of regional wall abnormalities.
* Patients with a history of non-breast malignancies are eligible if they have been disease-free for 5 or more years prior to randomization and are deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
* Special conditions for eligibility of lumpectomy patients: radiation therapy and surgery. Patients treated by lumpectomy must meet all the eligibility criteria in addition to the following:
* Generally, lumpectomy should be reserved for tumors less than 5 cm. However, at the investigator's discretion, patients treated with lumpectomy for tumors greater than or equal to 5 cm are eligible if eligibility criteria for lumpectomy are met.
* The margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. In patients for whom pathologic examination demonstrates tumor present at the line of resection, additional operative procedures may be performed to obtain clear margins. This is permissible even if axillary evaluation has been completed. Patients in whom tumor is still present at the resected margin after re-excision(s) must undergo total mastectomy to be eligible. (Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.)
* Irradiation of regional lymph nodes is optional, but plans for radiation therapy must be declared by the investigator prior to randomization for stratification purposes.
* Special conditions for eligibility of mastectomy patients: radiation therapy o Postmastectomy chest wall and/or regional nodal irradiation is optional. Plans for radiation in mastectomy patients must be declared by the investigator prior to randomization for stratification purposes.
Ineligibility Criteria
* Male patients are not eligible for this study. Women with one or more of the following conditions or prior therapies are also ineligible for this study:
* Tumor that has been determined to be human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
* Contralateral breast cancer (invasive or DCIS) or a mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant.
* Primary tumor staged as T4 for any reason.
* Clinical nodal stages including cN2b and cN3 or pathologic nodal stages including pN0(i+), pN2b, pN3b with clinically apparent internal mammary nodes, or pN3c.
* Suspicious nodes in the contralateral axilla or suspicious supraclavicular nodes. Patients with these conditions are considered ineligible unless there is biopsy evidence that these are not involved with tumor.
* Prior history of breast cancer, including DCIS (patients with a history of LCIS are eligible).
* Treatment, including radiation therapy, chemotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to randomization. One exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry. In such a case, hormonal therapy must stop at or before randomization and be re-started, if indicated, following chemotherapy. A second exception is radiation therapy for patients enrolled in NSABP B-39 and assigned to partial breast irradiation (Group 2). These patients may have received RT prior to B-38 study entry.
* Prior therapy with anthracyclines or taxanes for any malignancy.
* Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
* Therapy with any hormonal agents such as raloxifene (Evista®), tamoxifen, or other selective estrogen-receptor modulators (SERMs), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.
* Cardiac disease that would preclude the use of anthracyclines. This includes:
* history of myocardial infarction documented by elevated cardiac enzymes or regional wall abnormalities on assessment of left ventricular (LV) function;
* angina pectoris that requires the use of anti-anginal medication;
* any history of documented congestive heart failure;
* serious cardiac arrhythmia requiring medication;
* severe conduction abnormality;
* valvular disease with documented cardiac function compromise; and
* uncontrolled hypertension defined as blood pressure greater than 160/100 on antihypertensive therapy.
* Conditions that would prohibit administration of corticosteroids.
* Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0.
* Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from receiving any of the treatment options or would prevent prolonged follow-up.
* History of hepatitis B or C.
* Pregnancy or lactation at the time of proposed randomization. Women of reproductive potential must agree to use an effective non-hormonal method of contraception.
* Concurrent treatment with other investigational agents for the treatment of breast cancer.
* Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
* Special conditions for ineligibility of lumpectomy patients: radiation therapy and surgery
* For patients treated by lumpectomy, whole breast irradiation is required.
* The following patients will be ineligible:
* Patients with diffuse tumors (as demonstrated on mammography) treated with lumpectomy. (These patients are eligible if they undergo mastectomy.)
* Patients treated with lumpectomy in whom there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant. Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins.
* Patients in whom the margins of the resected specimen are involved with invasive tumor or DCIS.
Minimum Eligible Age
18 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
No
Sponsors
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National Cancer Institute (NCI)
NIH
Sponsor Role
collaborator
NSABP Foundation Inc
NETWORK
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Norman Wolmark, MD
Role: PRINCIPAL_INVESTIGATOR
NSABP Foundation Inc
Locations
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Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States
Site Status
Providence Cancer Center
Anchorage, Alaska, United States
Site Status
Robert and Carol Weissman Cancer Center at Martin Memorial
Stuart, Florida, United States
Site Status
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States
Site Status
South Shore Hospital
South Weymouth, Massachusetts, United States
Site Status
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States
Site Status
CCOP - Northern New Jersey
Hackensack, New Jersey, United States
Site Status
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States
Site Status
Altru Cancer Center at Altru Hospital
Grand Forks, North Dakota, United States
Site Status
Community Oncology Group at Cleveland Clinic Cancer Center
Independence, Ohio, United States
Site Status
Chestnut Hill Healthcare Cancer Center
Philadelphia, Pennsylvania, United States
Site Status
Madigan Army Medical Center - Tacoma
Tacoma, Washington, United States
Site Status
Countries
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United States
References
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Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. doi: 10.1200/JCO.2012.48.1275. Epub 2013 Aug 12.
Reference Type
DERIVED
Other Identifiers
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NSABP B-38
Identifier Type: -
Identifier Source: org_study_id
NCT00191958
Identifier Type: -
Identifier Source: nct_alias
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Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer
NCT00024102
COMPLETED
PHASE3
Combination Chemotherapy in Treating Women With Breast Cancer
NCT00003679
UNKNOWN
PHASE3
Combination Chemotherapy in Treating Women With Breast Cancer
NCT00003519
COMPLETED
PHASE3
Chemotherapy Followed by Surgery in Treating Women With Stage II or Stage III Breast Cancer
NCT00003953
COMPLETED
PHASE2
S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer
NCT00070564
ACTIVE_NOT_RECRUITING
PHASE3
Neoadjuvant Chemotherapy Using Doxorubicin and Paclitaxel in Treating Women With Large Breast Cancer
NCT00096291
COMPLETED
PHASE2
Combination Chemotherapy in Treating Women With Stage IIIB or Stage IV Breast Cancer
NCT00003352
COMPLETED
PHASE2
Primary Chemotherapy With Adriamycin/Cyclophosphamide(AC) vs Taxotere/Xeloda(TX) for Stage II and III Breast Cancer
NCT00352378
COMPLETED
PHASE3
Dose-Dense Docetaxel Before or After Doxorubicin/Cyclophosphamide in Axillary Node-Positive Breast Cancer
NCT00201708
COMPLETED
PHASE2
Doxorubicin Hydrochloride, Cyclophosphamide, and Pacltaxel With or Without Trastuzumab in Treating Women With HER2-Positive Node-Positive or High-Risk Node-Negative Breast Cancer
NCT00005970
COMPLETED
PHASE3
Combination Chemotherapy in Treating Women With Breast Cancer
NCT00047099
COMPLETED
PHASE3
Four Versus Six Cycles of Cyclophosphamide/Doxorubicin or Paclitaxel in Adjuvant Breast Cancer
NCT00041119
COMPLETED
PHASE3
Docetaxel, Doxorubicin, and Cyclophosphamide in Treating Women With Advanced Breast Cancer
NCT00074139
WITHDRAWN
PHASE1
Cyclophosphamide and Docetaxel or Doxorubicin in Treating Women With Newly Diagnosed Breast Cancer That Can Be Removed by Surgery
NCT00801411
UNKNOWN
PHASE2
Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel With or Without Carboplatin in Treating Patients With Triple-Negative Breast Cancer
NCT02488967
ACTIVE_NOT_RECRUITING
PHASE3
AZD2171 and Combination Chemotherapy in Treating Women With Locally Advanced Breast Cancer
NCT00310089
COMPLETED
NA
Adjuvant High-Dose, Sequential Chemotherapy in Treating Patients With Resected Breast Cancer
NCT00002679
COMPLETED
PHASE2
Doxorubicin and Docetaxel in Treating Women With Stage III Breast Cancer
NCT00005800
COMPLETED
PHASE2
Docetaxel in Node Positive Adjuvant Breast Cancer
NCT00688740
COMPLETED
PHASE3
Phase III Study of Two Different Schedules (Weekly and Tri-weekly) of Combination of Gemcitabine and Two Taxanes in MBC
NCT00236899
COMPLETED
PHASE3