CAPRI-3 Phase 3 clinical study to evaluate the use of continuing cetuximab treatment beyond first line progression in molecular selected metastatic colorectal cancer patients

Prior treatment

• Any contraindication to the use of cetuximab, bevacizumab, Irinotecan, 5-FU, oxaliplatin, folic acid.
• 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.
• 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).

Other illness

• History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.
• Marked proteinuria (nephrotic syndrome).
• Known history of alcohol or drug abuse.
• 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.

Age

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

Other

• 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.
• 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.

• Histologically proven diagnosis of colorectal adenocarcinoma.
• 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.
• Diagnosis of metastatic disease.
• Efficacy of a first line therapy containing anti-EGFR drug with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1) or a prolonged (at least 6 months) stable disease.
• Progression to first line therapy.
• RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis.
• RAS (NRAS and KRAS exon 2,3 and 4), BRAFV600E, PIK3CA, EGFR ECD wild-type and HER2 not amplified in liquid biopsy at the time of screening (according to NGS, Foundation/Roche).
• 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.