A PHASE IIIIII RANDOMIIZED TRIIAL OF FOLFOXIIRII + BEVACIIZUMAB VERSUS FOLFIIRII + BEVACIIZUMAB AS FIIRST-- LIINE TREATMENT FOR METASTATIIC COLORECTAL CANCER
- To compare the progression-free survival of bevacizumab in combination with
oxaliplatin, irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFOXIRI)
versus bevacizumab in combination with irinotecan hydrochloride, fluorouracil, and
leucovorin calcium (FOLFIRI) in patients with unresectable, metastatic colorectal
- To evaluate the safety profile, including long-term adverse events of these regimens in
- To compare the overall response rate, duration of response, and secondary R0 surgery
rates of metastases and overall survival between treatment arms.
- To evaluate potential surrogate markers predictive of bevacizumab activity.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance
status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center.
Patients are randomized to 1 of 2 treatment arms.
- Arm I (FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour,
oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on
day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on
- Arm II (FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour, leucovorin
calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive
fluorouracil IV continuously over 48 hours beginning on day 1.
In both arms, treatment repeats every 2 weeks for up to 12 courses. Treatment with
bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease
progression or unacceptable toxicity.
Patients undergo serum extraction and blood sample collection periodically for genotyping
studies. Patients also undergo collection of tumoral sections from paraffin embedded primary
and/or metastatic lesions periodically for immunohistochemical analyses.
After completion of study treatment, patients are followed every 8 weeks.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression free survival
To compare the progression free survival of bevacizumab in combination with oxaliplatin, irinotecan and infusional 5FU/LV ("GONO" FOLFOXIRI regimen) to bevacizumab in combination with irinotecan and infusional 5FU/LV (FOLFIRI regimen)
up to 54 months
Alfredo Falcone, MD
Presidio Ospedaliero di Livorno
Italy: Ethics Committee