Continuous or Intermittent Cetuximab Plus FOLFIRI as First-line Treatment in RAS/BRAF Wild-type mCRC Patients

Exclusion Criteria

• •1. Proof of a RAS or BRAF mutation (KRAS/NRAS exons 2, 3, 4 or BRAF exon 15) in the tumor (proven in the primary tumor or metastasis) or liquid biopsy during screening phase.
• •2. Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before written informed consent.
• •3. New York Heart Association Class III or greater heart failure by clinical judgement.
• •4. Myocardial infarction, balloon angioplasty (PTCA) with or without stenting, and cerebral vascular accident/stroke within the past 12 months before randomization
• •5. Unstable angina pectoris
• •6. Unstable cardiac arrhythmia \> grade 2 NCI CTCAE despite anti-arrhythmic therapy.
• •7. Active uncontrolled infection by investigator's perspective.
• •8. Pre-existing pulmonary fibrosis or immune pneumonitis
• •9. Additional cancer treatment (chemotherapy, radiation, immunotherapy or hormone treatment) during the study treatment in first-line and third-line treatment (treatments that are conducted as part of an anthroposophical or homeopathic treatment approach, e.g. mistletoe therapy does not represent an exclusion criterion)
• •10. Participation in a clinical study or experimental drug treatment within 30 days prior to written informed consent or within a period of 5 half-lives of the substances administered in a clinical study or during an experimental drug treatment prior to written informed consent, depending on which period is longest or simultaneous participation in another study while taking part in the study
• •11. Known hypersensitivity or allergic reaction to any of the following substances: 5-fluorouracil, folinic acid, cetuximab, irinotecan and chemically related substances and/or hypersensitivity to any of the components in the formulations of the aforementioned substances, including known hypersensitivity reactions to monoclonal antibodies NCI CTC grade ≥ 3.
• •12. Known hypersensitivity to Chinese hamster ovary cell (CHO) -cellular products or other recombinant human or humanized monoclonal antibodies
• •13. Patients with known brain metastases or leptomeningeal disease. In case of clinical suspicion of brain metastasis, a cranial CT or MRI must be performed to rule out brain metastasis before study inclusion.
• •14. History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune colitis or chronic diarrhea
• •15. Symptomatic peritoneal carcinosis
• •16. Severe, non-healing wounds, ulcers or bone fractures
• •17. Requirement for immunization with live vaccine including attenuated live vaccine from at least 4 weeks before begin of induction treatment until 6 months after the administration of IMPs.
• •18. Hemorrhagic diathesis or known thrombophilia
• •19. Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not required)
• •20. Treatment with nucleoside analogues including sorivudine or brivudine within 28 days before begin of induction treatment or requirement for concomitant antiviral treatment with sorivudine or brivudine or analogues
• •21. History of a second primary malignancy during the past 5 years before written informed consent or during participation in the study, with the exception of a basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, if these were treated curatively.
• •22. Active alcohol or drug abuse
• •23. Any significant adverse event that has not adequately resolved, severe acute or chronic concomitant disease or medical condition including psychiatric conditions (including recent i.e. within the past year or active suicidal ideation or behavior) or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• •24. Absent or restricted legal capacity
• •25. Patients who are institutionalized by order of court or public authority
• •26. Patients who might be dependent on the sponsor/investigator or the trial site