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
18 Years
75 Years
Both
Metastatic Colorectal Cancer
Trial Information
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
Target population:
Patients with histologically confirmed metastatic colorectal cancer progressed after a first
line treatment containing FOLFIRI and BEV
Inclusion criteria:
- 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
Endpoints:
- 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
Statistical methods:
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.
Inclusion Criteria:
- Age >18 <75 years of age
- Diagnosis of histologically proven adenocarcinoma of the colon or rectum, stage IV
- K-ras wild-type
- Performance Status (ECOG-PS) 0-1 at study entry
- Neutrophils ≥ 1.5 x 1039/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL
- Bilirubin level either normal or < 1.5 x upper limit of normal (ULN)
- Asparagine aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 X ULN (≤
5 x ULN if liver metastasis are present)
- Serum creatinine < 1.5 x ULN
- Effective contraception for both male and female patients
- Life expectancy of ≥ 3 months
- Signed written informed consent
Exclusion Criteria:
- History or presence of other disease, metabolic dysfunction, physical examination
finding, or clinical laboratory finding giving reasonable suspicion of a disease or
condition that contraindicates use of an investigational drug or patient at high risk
from treatment complications
- Other malignancies within the last 5 years (other than curatively treated basal cell
carcinoma of the skin and/or in situ carcinoma of the cervix)
- History of psychiatric disability judged by the investigator to be clinically
significant, precluding informed consent or interfering with compliance for oral drug
intake
- Known grade 3 or 4 allergic reaction to any of the components of the treatment
- Known drug abuse/ alcohol abuse
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall Survival
Outcome Time Frame:
the time from the date of randomisation to the date of death
Safety Issue:
Yes
Authority:
Italy: Ethics Committee
Study ID:
2007-006254-26
NCT ID:
NCT01030042
Start Date:
September 2009
Completion Date:
March 2014
Related Keywords:
- Metastatic Colorectal Cancer
- metastatic
- colorectal cancer
- two sequences therapy
- metastatic colorectal cancer patients progressed after a I line treatment containing FOLFIRI and BEV
- Colorectal Neoplasms
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