Clinical trial NCT00464646
Conditions: Breast Cancer
Keywords: NSABP Epirubicin Cyclophosphamide Docetaxel Trastuzumab Bevacizumab Neoadjuvant Therapy HER2 Locally Advanced Breast Cancer Adjuvant Therapy Pathologic Stage III Breast Cancer Inflammatory Breast Cancer
Sponsor: NSABP Foundation Inc
Start date: 2007-05-01; Completion date: 2014-05-01
Enrollment: 105 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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

Detailed description:
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.

Arms: arm 1: * 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
Interventions: intervention 1: Epirubicin intervention 2: Cyclophosphamide intervention 3: Docetaxel intervention 4: Trastuzumab intervention 5: Bevacizumab
Intervention descriptions: intervention 1: Both Cohorts: Epirubicin 90 mg/m2 IV every 21 days x 4 cycles intervention 2: Both Cohorts: Cyclophosphamide 600 mg/m2 IV every 21 days x 4 cycles intervention 3: Both Cohorts: Docetaxel 100 mg/m2 IV on Day 1 every 21 days x 4 cycles intervention 4: 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 intervention 5: 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

Protocol documents: