Bevacizumab is an angiogenesis inhibitor which means it works to stop blood vessel formation in tumors. Without new blood vessels, the growth of a tumor is slowed. Chemotherapy drugs kill cancer cells more directly. This study will evaluate: * How bevacizumab, given with chemotherapy before surgery, and then bevacizumab given alone after surgery, will affect locally advanced breast tumors * Side effects from adding bevacizumab to chemotherapy * Whether adding bevacizumab to chemotherapy for breast cancer will affect the heart * If receiving bevacizumab will have any effect on how patients recover from surgery * Side effects of the combinations of drugs used in this study
Initial trials of neoadjuvant chemotherapy administered for locally advanced tumors, including those in breast cancer, demonstrated therapy could induce sufficient tumor regression to allow for the resection of otherwise unresectable tumors. Subsequent demonstration of the equivalence of lumpectomy to mastectomy in patients with operable breast cancer, stimulated interest in the concept of using preoperative chemotherapy to reduce large, but operable, primary tumors to allow for lumpectomy in women who would otherwise require a mastectomy. Given the data from previous studies, it is appropriate to continue development of sequential doxorubicin/cyclophosphamide/docetaxel regimens to improve on clinical and pathologic response rates. FB-4 is a Phase II, single arm study for women with locally advanced human epidermal growth factor receptor 2 (HER2)-negative breast cancer diagnosed by core needle biopsy. The primary aim of the study is to determine the pathologic complete response rate in the breast following neoadjuvant chemotherapy combined with bevacizumab.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
15 mg/kg IV every 21 days x 4 cycles, then after clinical response assessment, 15 mg/kg IV every 21 days x 2 cycles, then following surgery, 15 mg/kg every 21 days x 10 cycles
60 mg/m\^2 IV every 21 days x 4 cycles
600 mg/m\^2 IV every 21 days x 4 cycles
Following clinical response assessment, 650 mg/m\^2 twice a day (orally), days 1-14 every 21 days x 4 cycles
Following clinical response assessment, 75 mg/m\^2 IV every 21 days x 4 cycles
NSABP Foundation, Inc.
Pittsburgh, Pennsylvania, United States
Pathologic Complete Response (pCR) in the Breast
Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen
Time frame: Approximately 7 months
pCR in the Breast and Nodes
Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel nodes
Time frame: Approximately 7 months
Clinical Response Rate (cRR) of the Sequential Regimen
Clinical tumor measurements were required before study entry \& before cycle 5 of chemotherapy (between AC \& TX). Final tumor measurements were obtained 4-5 weeks after the last dose of chemotherapy. Clinical tumor assessments by physical examination were recommended before each chemotherapy cycle. The criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee(RECIST) were used to define clinical response status. CR was defined as the disappearance of all lesions with no evidence of PD. PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions, using as reference the baseline sum longest diameter and/or the persistence of greater than or equal to 1 nontarget lesion without worsening of any other clinical manifestations of disease. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions, or unequivocal progression of existing lesions.
Time frame: Approximately 6 months
Reported Adverse Events
Number of Adverse Events
Time frame: Approximately 14 months
Cardiac Events
Events: Congestive Heart Failure; Cardiac Death
Time frame: Assessments throughout; up to 18 months following study entry
Progression-free Survival
Percentage of patients free from disease progression. Progression is determined using international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. At least a 20% increase in the sum of the longest diameter of the target lesions. Other manifestations of progressive disease would also be classified as disease progression, eg., appearance of one or more new lesions in the breast, regional lymph nodes or distant sites, unequivocal progression of existing non-target lesions, and appearance of inflammatory carcinoma on clinical exam.
Time frame: 2 years
Overall Survival
Percentage of patients alive.
Time frame: 2 years
Number of Patients With at Least One Surgical Complications (Wound Dehiscence, Infection, Seroma, or Hematoma).
Number of patients with at least one surgical complications (wound dehiscence, infection, seroma, or hematoma)
Time frame: Two (2) years
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