RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, 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 deliver cancer-killing substances to them. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells. PURPOSE: This randomized phase II trial is to see if docetaxel with or without bevacizumab followed by surgery, radiation therapy, and combination chemotherapy works better in treating patients who have stage III or stage IV breast cancer.
OBJECTIVES: * Determine the effect of bevacizumab and docetaxel on reduction of microvessel density and induction of apoptosis of endothelial and tumor cells in patients with locally advanced breast cancer. * Determine the safety profile of this regimen in these patients. * Compare the effect of docetaxel and bevacizumab, in terms of objective response, stabilization of disease, and progression-free survival, in these patients. OUTLINE: This is a randomized study. Patients are stratified according to disease stage. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8. * Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks. Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with estrogen and/or progesterone receptor-positive disease also receive oral tamoxifen daily for 5 years beginning after the completion of chemotherapy. Post-menopausal patients may receive oral anastrozole once daily for 5 years instead of tamoxifen. Patients are followed at 3, 6, and 12 months, every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Patients receive bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.
Approximately 4 weeks after the completion of radiotherapy, patients receive cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6.
Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks. Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
After the second course, patients with stable or responsive disease undergo modified radical mastectomy or breast-conserving surgery.
Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8. Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
Three to six weeks after surgery, patients undergo radiotherapy 5 days a week for 7 weeks.
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
UH-Southwest
Middleburg Heights, Ohio, United States
UH-Chagrin Highlands
Orange, Ohio, United States
UH-Green Road
South Euclid, Ohio, United States
UH-Westlake
Westlake, Ohio, United States
To evaluate the ability of bevacizumab and docetaxel to reduce microvessel density and induce apoptosis of endothelial and tumor cells.
The primary outcome measure is the difference in change in biologic parameters between the two arms. Tumor biopsies are required to perform pre- and post-treatment tumor microvessel density determination, apoptosis by TUNEL assay, proliferation markers by immunohistochemistry(e.g. PCNA, Ki-67), and expression of nuclear clusterin/XIP8.
Time frame: weeks 8 and 17
Number of patients with objective response
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Time frame: 5 years
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