MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab

Inclusion Criteria

• •Histologically confirmed, UICC stage IV adenocarcinoma of the left-sided colon or rectum with metastases (metastatic colorectal cancer), primarily non-resectable, confirmed RAS mutations proven in the primary tumor or metastasis (KRAS ans NRAS exon 2, 3, 4)
• •Age ≥ 18 years on day of signing informed consent
• •No previous chemotherapy for metastatic disease (1- 2 cycles FOLFIRI or mFOLFIRI are permitted before enrolment until RAS status is determined)
• •Patients suitable for chemotherapy administration
• •ECOG (Eastern Cooperative Oncology Group) status 0-1
• •Consent to liquid biopsy and mutation analysis
• •Estimated life expectancy \> 3 months
• •Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria (chest CT and abdominal CT 4 weeks or less before enrollment)
• •Adequate bone marrow function defined as: Leukocytes 3.0 x 10 9/L with neutrophils 1.5 x 10 9/L, Thrombocytes 100 x 10 9/L, Hemoglobin 9 g/dL
• •Adequate hepatic function defined as: Serum bilirubin 1.5 x ULN (Upper limit of normal), ALAT (Alanine-aminotransferase (= SGPT = serum glutamate pyruvate transaminase) and ASAT (aspartate-aminotransferase (= SGOT = serum glutamate oxalacetate transaminase) 2.5 x ULN (Upper limit of normal) (in the presence of hepatic metastases, ALAT and ASAT 5 x ULN)
• •Adequate renal function: Creatinine clearance ≥ 50 mL/min
• •Adequate cardiac function defined as Normal ECG and echocardiogram with a left ventricular ejection fraction (LVEF) of 55%
• •INR (International normalized ratio) \< 1.5 and aPTT (activated Partial thromboplastin time) \< 1.5 x ULN (patients without anticoagulation). Therapeutic anticoagulation is allowed if INR and aPTT have remained stable within the therapeutic range for at least 2 weeks.
• •Time interval of at least 6 months since last administration of any previous neoadjuvant/adjuvant chemotherapy or radiochemotherapy of the primary tumor in curative treatment intention to start of 1st line treatment
• •Any relevant toxicities of prior treatments must have resolved to grade ≤ 1 according to the CTCAE (version 5), except alopecia
• •Women of childbearing potential (WOCBP) should have a negative urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
• •Highly effective contraception for both male and female patients throughout the study and for at least 3 months after last dose of study medication administration if the risk of conception exists. Highly effective contraception has to be in line with the definition of the CTFG (Clinical Trial Facilitation Group) recommendation
• •Signed written informed consent and capacity of understanding the informed consent