The main purpose is to learn if adding bevacizumab to standard chemotherapy and trastuzumab to treat HER2-positive breast cancer will affect heart function. This study will evaluate: * How bevacizumab, given with chemotherapy, and then bevacizumab given with trastuzumab after surgery, will affect breast tumors * Side effects from adding bevacizumab to chemotherapy and trastuzumab * Whether adding bevacizumab to chemotherapy and trastuzumab for breast cancer will affect the heart * If receiving bevacizumab will have any effect on how patients recover from surgery
NSABP FB-5 is a Phase II study for women with HER2-positive invasive breast cancer evaluating a regimen of epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab and bevacizumab in two patient cohorts: * Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC) * Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer. The primary aims of the study are to determine the rate of cardiac events for all patients and the pCR rate in the breast and axillary lymph nodes for Cohort A. Cardiac events will be defined as NYHA Class III/IV congestive heart failure and cardiac death. For Cohort A, secondary aims of the study include determining the rate of pCR in the breast and the cCR rate following the neoadjuvant therapy. The secondary aims also include determining the value of the regimen in improving 5-year RFS and 5-year OS and determining the non-cardiac toxicities of the regimen in all patients. Patients in Cohort A will receive neoadjuvant therapy consisting of epirubicin plus cyclophosphamide (EC) every 21 days for 4 cycles plus bevacizumab given on Day 1 of Cycle 4 only, followed by docetaxel every 21 days for 4 cycles plus bevacizumab every 21 days for the initial 3 cycles. Patients will also receive weekly trastuzumab beginning with the first cycle of docetaxel and continuing until 1-7 days before surgery. Patients will then have breast surgery (lumpectomy or mastectomy) with axillary staging. Approximately 4-6 weeks following surgery, bevacizumab and trastuzumab will resume and continue every 3 weeks for 13 doses to complete one year of targeted therapy. Patients in Cohort B will receive adjuvant therapy consisting of EC every 21 days for 4 cycles followed by docetaxel every 21 days for 4 cycles. Beginning with the first cycle of docetaxel, patients will also receive bevacizumab every 21 days for 4 cycles and weekly trastuzumab until 3 weeks after the last docetaxel dose. Beginning 3 weeks after the last dose of docetaxel, both bevacizumab and trastuzumab will then be given every 3 weeks for 13 doses to complete 1 year of targeted therapy. Cardiac monitoring will be conducted for both cohorts. For Cohort A, LVEF assessments will be conducted at baseline, post-EC, 2-4 weeks following surgery (about 6 months from study entry), and 9, 12, 15, and 18 months from study entry. For Cohort B, LVEF assessments will be conducted at baseline, post-EC, and 6, 9, 12, 15, and 18 months from study entry. The preferred method for LVEF assessment is 2-D echocardiogram; however, LVEF assessment by MUGA scan is permitted. Patient follow-up will continue for 5 years following study entry. The FB-5 sample size is 105 patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
105
Both Cohorts: Epirubicin 90 mg/m2 IV every 21 days x 4 cycles
Both Cohorts: Cyclophosphamide 600 mg/m2 IV every 21 days x 4 cycles
Both Cohorts: Docetaxel 100 mg/m2 IV on Day 1 every 21 days x 4 cycles
Cohort A: Pre-op therapy - 4 mg/kg IV first dose, then subsequent doses at 2 mg/kg IV weekly (16+ weeks) until 1-7 days prior to surgery. Post-operative therapy (beginning no sooner than 28 days after surgery and continuing every 3 weeks x 13 doses) - 8 mg/kg IV first post-op dose, then subsequent doses at 6 mg/kg IV Cohort B: 4 mg/kg IV first dose, then subsequent doses at 2 mg/kg IV weekly on days 1, 8, and 15. Three (3) weeks after last dose of docetaxel, 6 mg/kg IV and continuing every 3 weeks x 13 doses
Cohort A: Cycles 1-4, 15 mg/kg IV on day 1 of cycle 4 only; Cycles 5-7, 15 mg/kg IV on day 1 every 21 days x 3 cycles; post-operative therapy (beginning no sooner than 28 days after surgery), 15 mg/kg IV every 3 weeks x 13 doses Cohort B: Cycles 5-8, 15 mg/kg IV on day 1 every 21 days x 4 cycles; beginning 3 weeks after last dose of docetaxel, 15 mg/kg IV every 3 weeks x 13 doses
Clearview Cancer Institute- Huntsville
Huntsville, Alabama, United States
Kaiser Permanente-San Diego
San Diego, California, United States
Kaiser Permanente-Vallejo
Vallejo, California, United States
CCOP, Colorado Cancer Research Program, Inc.
Denver, Colorado, United States
Baptist Regional Cancer Institute
Jacksonville, Florida, United States
Number of Patients With Pathological Complete Response (pCR) in the Breast and Nodes for Patients With HER2-positive LABC Following Neoadjuvant Treatment (Cohort A)
The determination of pCR is performed by the local pathologist following examination of tissue (breast and nodes)removed at the time of surgery. The outcome measure is the number of participants with no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or SNs identified after neoadjuvant chemotherapy.
Time frame: Assessed at time of surgery on average at 8 months
Number of Participants With Cardiac Events
The number of cardiac events defined as NYHA Class III/IV CHF and cardiac death.To determine the rate of cardiac events (NYHA Class III/IV CHF and cardiac death) of a regimen of EC followed by THA when administered to: Cohort A as neoadjuvant therapy for HER-2 positive locally advanced (clinical stage IIIA, IIIB or IIIC breast cancer or Cohort B as adjuvant therapy for resected HER2-positive pN2 or pN3 (pathologic stage III) breast cancer. The number of participants with one or more cardiac events are being reported.
Time frame: Cohort A: Baseline, post-treatment with EC, 2-4 weeks after surgery, and 9, 12, 15, and 18 months from study entry. Cohort B: Baseline, post-treatment with EC, 2-3 weeks after the last dose of docetaxel, and 6, 9, 12, 15, and 18 months from study entry.
Number of Participants With no Histologic Evidence of Invasive Tumor Cells in the Surgical Breast Specimen.
The determination of pCR will be performed by the local pathologist following examination of tissue (breast and nodes) removed at the time of surgery.
Time frame: Assessed at the time of surgery
Clinical Complete Response (cCR)
cCR following the last dose of docetaxel (Cohort A). cCR is detemined by tumor measurement by physical exam at baseline: target lesions greater than or equal to 2.0 cm; non-target lesions greater than or equal to 2.0 cm. cCR assessment at other timepoints: resolution of all target and non-target lesions identified at baseline, and no new lesions or other signs of disease progression.
Time frame: Determined at baseline, 2-3 weeks after the last EC dose, 2-4 weeks after last Docetaxel dose-before surgery.
Grade 3 and 4 Toxicities, Including Toxicities Associated With Radiation Therapy(RT)
Time frame: Before each cycle of pre-op Rx; 2-4 wks after the last docetaxel dose; 2-4 wks post surgery (Cohort A); every 6 wks during post-op Rx (Cohort A); every 6 wks during targeted therapy alone (Cohort B); RT complications assessed at 12 mos from study entry
Recurrence-free Survival
To determine the five-year RFS.
Time frame: From the first dose of study therapy until the date of recurrence or for a maximum of five (5) years from study entry
Overall Survival
Death from any cause during the 5 years from study entry.
Time frame: From the first dose of study therapy until the date of death or for a maximum of five (5) years from study entry
Percentage of Participants With Surgical Complications (From Mastectomy, Lumpectomy, and Axillary Staging Procedures) (Cohort A)
The percentage of patients with surgical complications (from mastectomy, lumpectomy, and axillary staging procedures).
Time frame: 2-4 weeks after surgery and at 9 and 12 months from study entry
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Rush University Medical Center
Chicago, Illinois, United States
CCOP, Central Illinois
Springfield, Illinois, United States
CCOP, Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
NortonHealtcare Inc.
Louisville, Kentucky, United States
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