Phase II Feasibility Trial Incorporating Bevacizumab Into Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Patients With Lymph Node Positive Breast Cancer

Brief Summary

Detailed Description

PRIMARY OBJECTIVES: I. To determine the incidence of clinically apparent cardiac dysfunction in patients with lymph node positive breast cancer treated with bevacizumab and dose dense doxorubicin/cyclophosphamide followed by paclitaxel (ddAC \> T). SECONDARY OBJECTIVES: I. To evaluate changes in LVEF during treatment. II. To evaluate non-cardiac toxicity. OUTLINE: This is a non-randomized, multicenter study. Patients are sequentially assigned to 1 of 2 treatment arms. Arm A: Patients receive doxorubicin IV, cyclophosphamide IV over 20-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SQ) on days 2-11 or pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients then receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1. Patients also receive G-CSF or pegfilgrastim as above. Treatment with paclitaxel, bevacizumab, and G-CSF or pegfilgrastim repeats every 14 days for 4 courses. Patients then receive bevacizumab alone every 14 days for up to 18 courses. Arm B: Patients receive doxorubicin, cyclophosphamide, and G-CSF or pegfilgrastim as in group I. Patients then receive paclitaxel, bevacizumab, and G-CSF or pegfilgrastim as in group I. Patients then receive bevacizumab alone every 14 days for up to 22 courses. Treatment in both groups continues in the absence of disease recurrence or unacceptable toxicity. Patients who require radiotherapy (post-lumpectomy) or who plan radiotherapy at the discretion of the investigator (post-mastectomy) undergo radiotherapy beginning within 6 weeks after the completion of chemotherapy. Premenopausal patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive disease receive oral tamoxifen once daily for 5 years beginning at the time of radiotherapy or within 6 weeks after the completion of chemotherapy. Postmenopausal patients with ER and/or PR positive disease receive an aromatase inhibitor (e.g., anastrozole, letrozole, or exemestane) or tamoxifen followed by an aromatase inhibitor once daily for up to 10 years. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years from study entry. ACCRUAL: A total of 226 patients (104 on arm A and 122 on arm B) were accrued for this study.

Primary Outcomes

Secondary Outcomes

• Proportion of Patients With Absolute Decrease in Left Ventricular Ejection Fraction (LVEF) Levels Post Doxorubicin and Cyclophosphamide(AC)(assessed on day 1 of cycles 5, 9, 17, 25, and at end of treatment)
• Proportion of Patients With Absolute Decrease in LVEF Levels Post Bevacizumab(assessed on day 1 of cycles 5, 9, 17, 25, and at end of treatment)