The main purpose of this study is to learn if adding bevacizumab to standard treatment with chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) for early stage HER2-negative breast cancer will prevent breast cancer from returning. A second purpose of this study is to learn if adding bevacizumab to treatment with chemotherapy will help women with HER2-negative breast cancer live longer. The researchers also want to learn about the side effects of the combination of drugs used in this study.
The B-46-I/07132 study, a multicenter, open-label, randomized Phase III, adjuvant therapy trial, will compare the value of adding bevacizumab to a non-anthracycline-based chemotherapy regimen relative to the same chemotherapy without bevacizumab and relative to an anthracycline-based chemotherapy regimen in women with resected node-positive or high-risk node-negative, HER2-negative breast cancer. This trial will determine whether the addition of bevacizumab to a regimen of docetaxel and cyclophosphamide (TCB) improves invasive disease-free survival relative to docetaxel and cyclophosphamide alone (TC). A secondary aim will be to determine whether the addition of bevacizumab to TC improves invasive disease-free survival compared to a regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC). Other secondary aims include whether TCB improves disease-free survival, overall survival, and recurrence-free interval relative to TC alone and to TAC. The toxicities of the three regimens will also be compared. Patients in the B-46-I/07132 study will be randomized to one of three treatment regimens: Group 1 patients will receive 6 cycles of TAC administered every 21 days (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); Group 2 patients will receive 6 cycles of TC administered every 21 days (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2); and Group 3 patients will receive 6 cycles of TCB every 21 days with bevacizumab therapy continuing every 21 days after completion of chemotherapy until 1 year following the first dose (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2, and bevacizumab 15 mg/kg). Primary prophylaxis with pegfilgrastim or filgrastim is required for Group 1 patients (optional for patients in Groups 2 and 3). Patients will also receive adjuvant radiation therapy as clinically indicated and endocrine therapy for hormone receptor-positive tumors. Tumor samples will be submitted for correlative science studies to evaluate predictors of study therapy benefit. Submission of a tumor sample is a study requirement for all patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,613
bevacizumab 15 mg/kg IV every 21 days for 6 cycles followed by bevacizumab 15 mg/kg IV every 21 days until 1 year following the first dose of bevacizumab
docetaxel 75 mg/m2 IV every 21 days for 6 cycles
doxorubicin 50 mg/m2 IV every 21 days for 6 cycles
Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles Group 2 and 3: cyclophosphamide 600 mg/m2 IV every 21 days for 6 cycles
pegfilgrastim 6 mg subcutaneous (SC) Day 2 every 21 days for 6 cycles \[filgrastim (Neupogen®) 5 mcg/kg Days 2-10 may be given in lieu of pegfilgrastim (Neulasta®), but pegfilgrastim is preferred.\]
Birmingham Hematology and Oncology
Bessemer, Alabama, United States
Birmingham Hematology and Oncology
Birmingham, Alabama, United States
Birmingham Hematology and Oncology - Brookwood
Birmingham, Alabama, United States
Birmingham Hematology and Oncology - Princeton
Birmingham, Alabama, United States
Birmingham Hematology and Oncology - Montclair
Birmingham, Alabama, United States
Invasive disease-free survival(IDFS)relative to the TAC chemotherapy regimen alone
Time frame: Every 12 months until recurrence
Invasive disease-free survival (IDFS) relative to the TAC chemotherapy regimen
Time frame: Every 12 months until recurrence
Disease-free survival (DFS-DCIS) relative to the TC alone regimen
Time frame: Every 12 months until recurrence
Overall survival (OS) relative to the TC alone regimen
Time frame: Every 12 months from randomization until death from any cause
OS relative to the TAC regimen
Time frame: Every 12 months from randomization until death from any cause
Recurrence-free interval (RFI) relative to the TC alone regimen
Time frame: Every 12 months, from randomization to local, regional, or distant recurrence
RFI relative to the TAC regimen
Time frame: Every 12 months, from randomization to local, regional, or distant recurrence
Develop molecular predictive markers for the degree of benefit from TCB over TC or TAC
Time frame: 6 years
Provide the efficacy data from Group 1 patients and Group 2 patients enrolled in B-46-I/07132 to US Oncology Research, Inc. (USOR) for a planned combined analysis with efficacy data from patients receiving the same regimens in the USOR 06-090 trial
Time frame: 10 years
Toxicity associated with each of the regimens
Time frame: Every 6 months
Determine the role of topoisomerase II alpha (TOP2A) in prognosis and prediction of degree of benefit from TAC over TC
Time frame: 6 years
Develop predictive markers for benefit from doxorubicin
Time frame: 6 years
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