Testing a Functional Precision Medicine Approach to Select Chemotherapy for Metastatic Colorectal Cancer (COSENSE-1)

Inclusion criteria

• General conditions:
• Age 18 or older
• ECOG performance status 0 or 1
• Obtained informed consent
• Acceptable organ function (defined in publicly available protocol)
• Women of child-bearing potential and men must agree to use highly effective contraception (defined in publicly available protocol)
• Disease and treatment specific conditions:
• Histologically confirmed pMMR/MSS adenocarcinoma originating from the colon or rectum
• Unresectable metastatic disease (not amenable to radical surgery of the cancer disease at the time of study inclusion)
• Patient has metastatic or primary lesion available for biopsy
• Patient has measurable or evaluable disease per RECIST (version 1.1)
• The oxaliplatin-based regimen FOLFOX (+/- antibody) versus the irinotecan-based regimen FOLFIRI (+/- antibody), are evaluated by an experienced physician, independent of inclusion in the trial, to be equally recommended for the participant as standard of care first-line therapy in the treatment of mCRC, following the Norwegian national guideline on the treatment of colorectal cancer (https://www.helsedirektoratet.no/retningslinjer/kreft-i-tykktarm-og-endetarm-handlingsprogram)
• Patient is eligible for full (100%) chemotherapy doses at first treatment cycle
• Treatment with chemotherapy can be scheduled within 28 days from referral

Exclusion criteria

• Patient has metastatic MMR deficient/MSI adenocarcinoma
• Patient is ineligible for full (100%) chemotherapy doses at first treatment cycle
• Patient is not equally eligible for FOLFOX (+/- antibody) and FOLFIRI (+/- antibody) chemotherapy regimens, according to the Norwegian national guideline on the treatment of colorectal cancer
• ECOG performance status 2 or worse
• Pregnancy or planned pregnancy during the study period, due to the risks of drug treatment to a developing foetus
• Breastfeeding
• Patients with psychological, geographical, familial or sociological conditions that can prevent compliance with the study protocol
• Inability to understand study procedures and comply with them, or disorder that compromises the patient's ability to provide informed consent and/or comply with study procedures
• Patient fulfils any of the contraindications listed in the SmPC of the relevant IMP
• Treatment cannot be scheduled within 28 days from referral
• Medical history:
• Partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
• Evidence of CNS metastasis
• Unresolved toxicities of a previous systemic treatment that, in the opinion of the physician, make the patient unfit for inclusion
• Antitumoural treatment ≤ 30 days before inclusion. Hormonal substitutive treatment is allowed
• Preexisting significant cardiovascular disease including uncontrolled/unstable or symptomatic angina, uncontrolled atrial or ventricular arrythmias, LVEF known to be \< 40% or symptomatic congestive heart failure
• Stroke (including TIA) or acute myocardial infarction within 6 months before the first dose of study treatment
• Clinically significant peripheral sensory neuropathy
• Recent (\<6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or another significant thromboembolic event
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on chest computed tomography (CT)
• Evidence of previous acute hypersensitivity reaction to any component of the treatment
• History of any disease that may increase the risks associated with study participation