Study to Evaluate the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab.

Inclusion Criteria

• Signed written informed consent
• Inpatient or outpatient ≥ 18 years of age
• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
• First occurrence of metastatic disease (not curatively resectable)
• Presence of at least one lesion measurable uni dimensionally by computerised tomography (CT) scan or magnetic resonance imaging (MRI). (Target lesion(s) must not lie within an irradiated area)
• Life expectancy of ≥ 3 months
• Karnofsky performance status of ≥ 60, at study entry
• White blood cell count (WBC) ≥ 3 x 10^9/L, with neutrophils ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, and hemoglobin ≥ 9 g/dL
• Aspartate transaminase and alanine transaminase ≤ 2.5 x Upper Limit of Normal (ULN) (≤ 5 x ULN if liver metastasis are present)
• Normal serum creatinine (in case of elevated creatinine, labelled ethylenediaminetetraacetic acid clearance ≥ 65 mL/min is acceptable)
• Effective contraception for both male and female subjects if the risk of conception exists
• Tumor biopsy or archived sample available

Exclusion criteria

• Brain metastasis and/or leptomeningeal disease (known or suspected)
• Previous chemotherapy for colorectal cancer except adjuvant treatment with progression of disease documented > 6 months after end of adjuvant treatment.
• Previous oxaliplatin-based chemotherapy
• Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to randomization
• Concurrent or previous chronic systemic immune therapy, targeted therapy, anti-vascular epithelial growth factor (VEGF) therapy, epidermal growth factor receptor (EGFR) pathway targeting therapy not indicated in the study protocol
• Concurrent hormonal therapy not indicated in the study protocol except for physiologic replacement or contraception
• Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
• Peripheral neuropathy >grade 1
• Known hypersensitivity reaction to any of the components of the treatment.
• Any concurrent malignancy other than basal cell cancer of the skin, or pre-invasive cancer of the cervix. (Subjects with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the study)
• Pregnancy (absence to be confirmed by ß-human chorionic gonadotrophin test) or lactation period
• Known drug abuse/alcohol abuse
• Legal incapacity or limited legal capacity
• Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent
• Participation in another clinical study within the 30 days before randomization
• Significant disease which, in the investigator's opinion, would exclude the subject from the study