CAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio-marker Driven Cetuximab-based Treatment Regimen

Prior treatment

• Any contraindication to the use of cetuximab, Irinotecan, 5-FU, oxaliplatin, folinic acid,bevacizumab, trifluridine-tipiracil, regorafenib
• Myocardial infarction, unstable angina pectoris, balloon angioplasty (PTCA) with or without stenting within the past 12 months before inclusion in the study, Grade III or IV heart failure (NYHA classification)
• Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
• Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study
• A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study

Other illness

• Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease
• Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix
• Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
• History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
• Uncontrolled hypertension
• Marked proteinuria (nephrotic syndrome)
• Known history of alcohol or drug abuse

Age

• Fertile women (\<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception•

Other

• Pregnancy (exclusion to be ascertained by a beta hCG test)
• Breastfeeding
• Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
• Known or clinically suspected brain metastases
• Severe, non-healing wounds, ulcers or bone fractures
• Known DPD deficiency (specific screening not required)
• Absent or restricted legal capacity

• Histologically proven diagnosis of colorectal adenocarcinoma
• Diagnosis of metastatic disease
• RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis
• Measurable disease according to Response Evaluation Criteria in Solid Tumors RECIST criteria, vers.1.1)
• Male or female patients ≥ 18 years of age
• ECOG Performance Status 0,1
• Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment as defined by the following parameters:
  • Bone marrow:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Platelets ≥ 100 x 109/L
  • Liver function:
  • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and ALT (SGPT) ≤ 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN
  • Renal function:
  • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
• If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment
• If female and of childbearing potential, or if male, agreement to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 3 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate
• Signed informed consent obtained before screening.