AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE III STUDY OF SECOND-LINE CHEMOTHERAPY WITH OR WITHOUT BEVACIZUMAB IN METASTATIC COLORECTAL CANCER PATIENTS WHO HAVE RECEIVED FIRST-LINE CHEMOTHERAPY PLUS BEVACIZUMAB.
- To compare the progression-free survival of second-line chemotherapy with or without
bevacizumab in patients with metastatic colorectal cancer who have received first-line
chemotherapy with bevacizumab.
- To compare the overall survival, response rate, and safety profile of second-line
chemotherapy of these regimens in these patients.
- To conduct pharmacogenomics assessment of candidate variants in the VEGF gene and
evaluate their association with progression-free survival and other study outcomes.
OUTLINE: This is a multicenter study. Patients are stratified according to participating
center, ECOG performance status (0 vs 1-2), disease-free interval from the last
administration of first-line chemotherapy for metastatic disease (≤ 3 months vs > 3 months),
and type of second-line chemotherapy (irinotecan hydrochloride, leucovorin calcium, and
fluorouracil [FOLFIRI] vs oxaliplatin, leucovorin calcium, and fluorouracil [mFOLFOX-6]).
Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over
1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and
fluorouracil IV over 46 hours continuously beginning on day 1.
- Arm II: Patients receive combination chemotherapy as in arm I and bevacizumab IV on day
Treatment in both arms repeats every 2 weeks for up to 12 courses in the absence of disease
progression or unacceptable toxicity.
Existing formalin-fixed paraffin-embedded tumor tissue samples are assessed for
pharmacogenomics and markers predictive of response, resistance to, or toxicity from
bevacizumab. Samples are analyzed via RT-PCR, array comparative genomic hybridization,
fluorescence in situ hybridization, sequencing of candidate genes, and immunohistochemistry.
After completion of study treatment, patients are followed for 1 year.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
last progression of the last patient
Alfredo Falcone, MD
Presidio Ospedaliero di Livorno
Italy: Agenzia Italiana del Farmaco (AIFA)