Synopsis - PETACC 8 Page 1 of 2
Title: “Adjuvant treatment of fully resected stage III colon cancer with FOLFOX-4 plus
Cetuximab vs FOLFOX-4”
Title of study PETACC 8: ADJUVANT TREATMENT OF FULLY RESECTED STAGE III COLON
CANCER WITH FOLFOX-4 PLUS CETUXIMAB VERSUS FOLFOX-4
Study Endpoints • Primary: Disease free survival
- Disease free survival rate at 3 years
- Overall survival curves
- Treatment compliance
- 5-year overall survival rate
- Biological study for evaluation of markers predictive for relapse and/or treatment
Main Inclusion - Age ≥ 18 and <75
Criteria - Pathologically confirmed stage III colon adenocarcinoma, regardless of EGFR
- Curative R0 resection performed not less than 28 and not more than 56 days prior to
- No metastatic spread at baseline assessment
- No prior chemotherapy
- No prior abdominal or pelvic irradiation
- WHO performance status: 0, 1 or 2
- Signed written informed consent obtained prior to any study specific screening
- Patients with childbearing potential should use effective contraception
Main Exclusion - Distant metastatic disease
Criteria - Inflammatory bowel disease
- Rectal cancer located within 15 cm from the anal verge by endoscopy or above the
peritoneal reflection at surgery or having received radiation therapy prior to surgery
- Pregnant or breast-feeding woman
- Known hypersensitivity reaction to any of the components of study treatments.
Study design and This open randomized, controlled, multinational/multicenter European phase III study is
treatment plan setting to evaluate the efficacy of cetuximab in addition to FOLFOX-4 for 6 months in
patients with fully resected colon cancer.
Arm A: Cetuximab (400 mg/m² first infusion then 250 mg/m² weekly) + FOLFOX-4.
Arm B: FOLFOX-4 alone, patients will thus receive FOLFOX-4 alone.
The cycle duration in Arms A and B is 14 days (2 weeks) with a total of 12 planned
cycles (24 weeks). Patients will be followed for recurrence/new occurrence of colon
cancer and survival.
Randomization will be stratified according to:
No obstruction and no perforation vs obstruction and/or perforation
T1-3 vs T4
N1 vs N2.
Time for Randomization: D 28 to D 56 after surgery. Maximal period between
randomization and treatment = 14 days.
Page 2 of 2
Statistical methods The primary analyses of efficacy will be performed on intent-to-treat principle, i.e., data
from all randomized patients (EGFR+ and EGFR-) will be analyzed according to
treatment assigned at randomization. Subgroup analysis will be performed on patients
with EGFR + and EGFR - tumors as exploratory analyses.
The safety data will be presented for all patients who start treatment, summarized
according to the actual treatment received.
Time to event (disease free and overall survival) will be measured from the date of
Patients who have not experienced the event at the date of last follow-up assessment.
Disease free survival and survival curves will be estimated using the Kaplan-Meier
According to treatment arms, DFS and overall survival curves will be compared using a
stratified two-sided Log-rank test. Treatment comparison will be performed according to
treatment assigned at randomization. To adjust for potential confounding variables and
stratification variables, Cox proportional hazards model will be used. All tests will be
performed two-sided at a significance level of 5%.
The safety data of the different infusional schedules will be evaluated separately and
compared using the Kruskal-Wallis test.
A 23 percent reduction in the risk of disease recurrence or death (HR = 0.771) is
expected between the two treatment arms of the trial. This estimate is obtained based
on an absolute gain of 5.6% at 3 years DFS, from 72.2 % (control arm) to 77.8%
(experimental arm). 1900 patients will need to be enrolled to observe the 626 necessary
events with α= 5% and β= 10% assuming an exponential distribution for the DFS
curves (two-sided stratified Logrank test). Assuming a 5% drop-out rate per year, it will
be necessary to include 100 extra patients, in order to attain the necessary power for a
statistical comparison of the disease rates, resulting in a total of 2000 patients
Evaluation of safety data will be performed by an Independent Data Monitoring
Committee (IDMC) at regular intervals while the study is ongoing.
Accrual rate per year : 667 patients
Estimated Accrual duration: 3 years
Estimated trial duration to observe the 626 necessary events to achieve
the statistical power : 6 years ( 5.7 years)
Planned study period Overall study duration (including follow-up): November 2005 - November 2011 (6
Target recruitment period: November 2005 - November 2008 (3 years)
No efficacy interim analysis is planned, the results will thus be analysed after study
Follow-up duration per subject: 3.0 to 6.0 years
Final analysis: 6.0 years
Overall Survival analysis : 9 years