Correction of participating countries, provision of details of all involved groups and country coordinating investigators (changed for Austria and Germany) Provision of clear definitions of the conditions to be fulfilled and the expected time points for primary and final analyses, clarification of definition of end of trial Clarification of visit and assessment schedule At the request of the IDMC, introduction of electrolyte measurement at baseline, 3 months, 6 months after start of treatment, at the end of treatment Visit and at the second follow-up visit (12 months after surgery) if still abnormal Clarification of time intervals for colonoscopy Update of pretreatment recommendations before cetuximab administrations: addition of corticosteroid Clarification of dosage reduction and treatment continuation rules Harmonization of description of the adverse events page with the CRF Update of informed consent based on changes introduced by this amendment (main study and for translational research) Update of planned statistical analyses Correction of errors

* Addition of a second primary objective, namely the comparison of treatments in patients with KRAS wild type tumors • Adjustment of the risk reduction (hazard ratio) expected from the addition of cetuximab, in the entire study population. • Implementation of one interim analysis for the entire study population and one for the population of patients with KRAS wild type tumors • Increase of the total sample size from 2000 to 2842 patients to achieve the necessary number of events for the primary statistical analysis within a reasonable time frame, considering the adjustments of the individual alpha required because of two primary endpoints and the implementation of interim analysis and the need to maintain the original power of 90%. • Update of the planned statistical analyses and related assumptions, considering the additional primary objective • Introduction of retrospective KRAS assessment in all patients • Clarification of time interval between curative R0 resection and start of treatment • Update of the Patient Information based on introduction of KRAS assessment (main study) • Update of the handling instructions and compatibility of cetuximab with various infusion set materials

• Introduction of an inclusion criterion regarding KRAS status. • Introduction of prospective KRAS assessment in all new patients. The specific logistics are described in a separate document. • The only primary objective will be the comparison of disease free survival (DFS) between the two treatment arms in the population of patients with KRAS wild-type tumors. • Addition of a new secondary objective, namely the comparison of DFS in the entire population of all patients randomized up to 24:00h, 17 June 2008 (to be performed only if a significant effect on DFS, in the KRAS wild-type population is seen). • Interim analysis only for the primary objective in patients with a KRAS wild-type tumor. • In total 2099 patients have been included until the recruitment stop on 17 June 2008, of whom an estimated 957 patients have assessable KRAS wild-type tumors. An additional 450 patients with a KRAS wild-type tumor should be included to achieve the necessary number of events for the primary statistical analysis, within a reasonable time frame. Therefore, it is estimated that 825 patients will need to be assessed for the KRAS status of their tumors after the restart of patient enrollment (assuming 57.5% will be KRAS wild-type and there will be 5% withdrawals, for other reasons, prior to randomization). • Prolongation of the survival follow-up to 7 years after randomization of the last patient (i.e. 10.5 years in total assuming a recruitment period of 3.5 years). • Update of the planned statistical analyses and related assumptions, considering the population change for primary analysis. • Update of the Patient Information based on introduction of KRAS assessment (main study) and introduction of a new patient information and informed consent necessary for the prescreening of patients for KRAS status. • Update of Translational Research sections • Corrections of errors

Change of an inclusion criterion regarding the age of the patients. The FFCD has decided to follow the additional DSMB recommendations regarding patients aged 71 or older which has strongly recommended taking a precautionary measure, no longer to include patients aged 71 or older (at screening), because of an increased risk of toxicity or death observed in the population > 70 years old in the PETACC8 study as compared to the population < 71 years old, whatever the treatment arm is. Furthermore, these results are in line with the analysis of the ACCENT database presented at the main ASCO meeting (2009) that support the use of 5-FU-based regimens without Oxaliplatin in elderly patients >70 years old (McCleary et al., ASCO 2009).