Cetuximab Standard or Dose Escalation in First Line Colorectal Cancer

Inclusion Criteria

• Written informed consent (+ optional for PK and TR) must be given according to ICH/GCP and national/local regulations.
• Patient is at least 18 years of age.
• Patient's body weight is ≤ 120 kg.
• Histologically proven and measurable (RECIST criteria v.1.1) metastatic adenocarcinoma of the colon or rectum, not in a previously irradiated area.
• K-Ras wild type tumour eligible for treatment with cetuximab.
• Unresectable metastatic disease.
• Life expectancy of at least 12 weeks.
• WHO ECOG performance status: 0 or 1.
• Effective contraception for both male and female patients if the risk of conception exists.
• Adequate organ function.
• Adequate bone marrow, hepatic and renal function (assessed within 14 days prior to study entry):
• Hemoglobin > 10.0 g/dL, absolute neutrophil count > 1.5 x 109/L, platelet count > 100 x 109/L
• ALAT, ASAT 50 mL/min (calculated according to Cockroft and Gault)

Exclusion Criteria

• Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 6 months prior to registration on study).
• Prior treatment with EGFR inhibitor or chemotherapy with irinotecan in adjuvant settings.
• Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry.
• Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment.
• Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol.
• Any active dermatological condition > grade 1.
• Brain metastasis (known or suspected).
• Significant impairment of intestinal absorption (e.g. chronic diarrhea, inflammatory bowel disease).
• Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection.
• Uncontrolled coronary artery disease and/or unstable angina, a history of a myocardial infarction within the last 12 months or heart failure NYHA class III or IV. High risk of uncontrolled arrhythmia.
• Known allergy or any other adverse reaction to any of the drugs or to any related compound.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Gilbert disease.
• Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
• Organ allografts requiring immunosuppressive therapy.
• Pregnancy (absence confirmed by serum/urine beta human choriongonadotrophin in pre-menopausal women) or breast-feeding.
• Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.