A Phase III Clinical Trial Comparing the Combination of TC Plus Bevacizumab to TC Alone and to TAC for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer
Overview
- Phase
- Phase 3
- Intervention
- docetaxel
- Conditions
- Breast Cancer
- Sponsor
- NSABP Foundation Inc
- Enrollment
- 1613
- Locations
- 497
- Primary Endpoint
- Invasive disease-free survival(IDFS)relative to the TAC chemotherapy regimen alone
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be female.
- •The patient must be greater than or equal to 18 years of age and less than or equal to 70 years of age.
- •The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
- •The breast cancer must be HER2-negative based on current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. If the result of the in situ hybridization testing (FISH, chromagen in situ hybridization (CISH), or other) is equivocal, the patient is eligible if there is no plan to administer HER2-targeted therapy.
- •All of the following staging criteria (according to the 6th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual) must be met: By pathologic evaluation, primary tumor must be pT1-3; By pathologic evaluation, ipsilateral nodes must be pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b. If pN0, at least one of the following criteria must be met: ER negative and PgR negative; or Pathologic tumor size greater than 2.0 cm; or T1c (pathologic tumor size greater than 1.0 cm but less than or equal to 2.0 cm) and ER positive (PgR status may be positive or negative) and either Oncotype DX® Recurrence Score of greater than or equal to 25 or grade 3 histology.
- •Patients must have undergone either a total mastectomy or breast-conserving surgery (lumpectomy).
- •For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures must be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. (Patients with margins positive for lobular carcinoma in situ \[LCIS\] are eligible without additional resection.)
- •For patients who undergo mastectomy, margins must be histologically free of invasive tumor and DCIS.
- •Patients must have completed one of the following procedures for evaluation of pathologic nodal status: Sentinel lymphadenectomy alone if pathologic nodal staging based on sentinel lymphadenectomy is pN0, pN1mi, or pN1b; Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes if the sentinel node (SN) is positive; or Axillary lymphadenectomy without SN isolation procedure.
Exclusion Criteria
- •T4 tumors including inflammatory breast cancer.
- •Definitive clinical or radiologic evidence of metastatic disease.
- •Synchronous or metachronous contralateral invasive breast cancer. (Patients with synchronous and/or metachronous contralateral DCIS are eligible.)
- •Any history of ipsilateral invasive breast cancer or ipsilateral DCIS.
- •History of non-breast malignancies within 5 years prior to randomization, except for the following: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinomas of the skin.
- •Previous therapy with anthracyclines, taxanes, or bevacizumab for any malignancy.
- •Chemotherapy administered for the currently diagnosed breast cancer prior to randomization.
- •Continued therapy with any hormonal agent such as raloxifene or tamoxifen (or other SERM) or an aromatase inhibitor. (Patients are eligible if these medications are discontinued prior to randomization.)
- •Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy. Patients are eligible if these medications are discontinued prior to randomization.
- •Active hepatitis B or hepatitis C with abnormal liver function tests.
Arms & Interventions
Group 1: TAC then pegfilgrastim
docetaxel, doxorubicin, cyclophosphamide, and pegfilgrastim/filgrastim
Intervention: docetaxel
Group 1: TAC then pegfilgrastim
docetaxel, doxorubicin, cyclophosphamide, and pegfilgrastim/filgrastim
Intervention: doxorubicin
Group 1: TAC then pegfilgrastim
docetaxel, doxorubicin, cyclophosphamide, and pegfilgrastim/filgrastim
Intervention: cyclophosphamide
Group 1: TAC then pegfilgrastim
docetaxel, doxorubicin, cyclophosphamide, and pegfilgrastim/filgrastim
Intervention: pegfilgrastim
Group 2: TC
docetaxel and cyclophosphamide
Intervention: docetaxel
Group 2: TC
docetaxel and cyclophosphamide
Intervention: cyclophosphamide
Group 3: TC + bevacizumab
docetaxel, cyclophosphamide, and bevacizumab
Intervention: bevacizumab
Group 3: TC + bevacizumab
docetaxel, cyclophosphamide, and bevacizumab
Intervention: docetaxel
Group 3: TC + bevacizumab
docetaxel, cyclophosphamide, and bevacizumab
Intervention: cyclophosphamide
Outcomes
Primary Outcomes
Invasive disease-free survival(IDFS)relative to the TAC chemotherapy regimen alone
Time Frame: Every 12 months until recurrence
Secondary Outcomes
- Toxicity associated with each of the regimens(Every 6 months)
- RFI relative to the TAC regimen(Every 12 months, from randomization to local, regional, or distant recurrence)
- Invasive disease-free survival (IDFS) relative to the TAC chemotherapy regimen(Every 12 months until recurrence)
- Overall survival (OS) relative to the TC alone regimen(Every 12 months from randomization until death from any cause)
- OS relative to the TAC regimen(Every 12 months from randomization until death from any cause)
- 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(10 years)
- Determine the role of topoisomerase II alpha (TOP2A) in prognosis and prediction of degree of benefit from TAC over TC(6 years)
- Develop predictive markers for benefit from doxorubicin(6 years)
- Disease-free survival (DFS-DCIS) relative to the TC alone regimen(Every 12 months until recurrence)
- Recurrence-free interval (RFI) relative to the TC alone regimen(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(6 years)