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

A Randomized, Open-label Phase II Study Evaluating the Efficacy and Safety of FOLFOX-4 Plus Cetuximab Versus UFOX Plus Cetuximab as First-line Therapy in Subjects With Metastatic Colorectal Cancer.

This is an exploratory study to compare activity and safety in 400 patients with previously untreated metastatic carcinoma of the colon treated with UFOX (a combination regimen of UFT® (Tegafur plus Uracil), Oxaliplatin, Folinic Acid) plus Cetuximab or FOLFOX-4 (a combination regimen of 5 Fluorouracil (5-FU), Oxaliplatin and Folinic Acid) 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