Open-label Randomized, Parallel Group, Phase III, Multicenter Trial Comparing Two Different Sequences of Therapy (Irinotecan/Cetuximab Followed by Fluorouracil/Leucovorin With Oxaliplatin (FOLFOX-4) vs FOLFOX-4 Followed by Irinotecan/Cetuximab) in Metastatic Colorectal Patients Treated With Fluorouracil/Leucovorin With Irinotecan FOLFIRI /Bevacizumab as First Line Chemotherapy
Patients with histologically confirmed metastatic colorectal cancer progressed after a first
line treatment containing FOLFIRI and BEV
- Age >18 < 75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- ECOG performance status 0-1 at study entry
- Response Rate, Disease control rate, The duration of overall response, Overall survival,
PFS, Time to treatment failure, Quality of Life, Incidence of AEs, Frequency and nature of
serious adverse reactions (SADRs), Premature withdrawals
Assuming a randomization ratio of 1:1, 282 deaths are required in order to achieve a power
of 80% of detecting a hazard ratio of 0.72 in favour of one of the two sequences,
translating in an increase of median survival time from 10 to 14 months, with a type I error
of 5%, two-sided, using the Mantel-Cox version of the log-rank test. With a uniform accrual
period of 3 years and a follow-up of 18 months, about 350 patients will be needed to reach
the target number of events.
All statistical analyses will be based on an intention-to-treat approach. CONSORT rules will
be applied to describe study flow and protocol deviations.
All OS and PFS curves will be drawn with the Kaplan-Meier method. Results will be presented
as Hazard Ratio (HRs) and their 95% Confidence Interval (CIs).
On annual basis, starting from the second year, an interim analysis will be conducted. In
principle, no formal stopping rule will be applied, unless otherwise suggested by the DSMC.
Safety reports will be drawn on annual basis.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
the time from the date of randomisation to the date of death
Italy: Ethics Committee