A Randomized, 2x2 Factorial Design Biomarker Prevention Trial of Low-dose ASA and Metformin in Stage I-III Crc Patients

Inclusion Criteria: * Patients aged \> 18 and ≤ 80 years. * Patients with completely resected stage I, II, or III primary colorectal cancer within 24 months prior to randomization, regardless of (neo-)adjuvant chemotherapy. Patients with pT1 CRC treated with endoscopic polypectomy. * Adjuvant chemotherapy and (neo-)adjuvant radiotherapy terminated at least 3 months before randomization. * ECOG performance status ≤ 1. * Satisfactory hematological and biochemical functions: * Platelets ≥ 100 x 10\^9/L * Creatinine clearance estimated with the Cockcroft - Gault formula ≥ 60 mL/min. Patients with Gault formula ≥ 45-59 ≤ ml/min are eligible but they will receive a single (evening) tablet of MET, 850 mg. * AST and ALT ≤ 2.5 times ULN. * Females of childbearing potential/males with partners of childbearing potential participating in the study are to use effective methods of birth control during study participation. Female participants must provide a pregnancy test, according to local/national guidelines. * Able to understand and sign an informed consent (or have a legal representative who is able and willing to do so). Exclusion Criteria: * Patients who are not able to undergo colonoscopy. * Patients who are allergic or intolerant to ibuprofen or naproxen,or who have MET-, or ASA-, or salicylate intolerance or more generalized drug intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). * Any serious medical condition, laboratory abnormality, or psychiatric illness …