Safety and Tolerability of Bevacizumab Plus Paclitaxel vs. Bevacizumab Plus Metronomic Cyclophosphamide and Capecitabine as First-Line Therapy in Patients With HER2-Negative Metastatic or Locally Recurrent Breast Cancer - A Multicenter, Randomized Phase III Trial
- To determine if bevacizumab and paclitaxel versus bevacizumab, metronomic
cyclophosphamide, and capecitabine as first-line therapy causes less medication-related
adverse events in women with HER2-negative metastatic, locally advanced, or recurrent
- To compare quality of life (QOL) in patients treated with these regimens.
- To replicate previous findings of better QOL in patients with complete response or
partial response versus stable disease for 6 months or greater.
- To determine the predictive value of baseline QOL for the duration of a meaningful
change in QOL of patients treated with chemotherapy.
- To determine the associations between the QOL endpoints, selected health economics, and
OUTLINE: This is a multicenter study. Patients are stratified according to tumor response
(measurable vs evaluable disease), WHO performance status (0 or 1 vs 2), and center.
Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and
paclitaxel IV on days 1, 8, and 15. Treatment repeats every 4 weeks in the absence of
disease progression or unacceptable toxicity.
- Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral
cyclophosphamide once daily on days 1-28, and oral capecitabine 3 times a day on days
1-28. Treatment repeats every 4 weeks in the absence of disease progression or
Patients complete quality-of-life questionnaire (BL-QA) and health economics questionnaires
(BL-HEA and EQ-5D) at baseline, during, and after completion of study therapy.
After completion of study treatment, patients are followed up at 1 month, every 3 months for
1 year, and then every 6 months for 1 year.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of grade 3-5 adverse events
Documentation of AE observed during trial treatment and in follow-up until resolution
Christoph Rochlitz, MD