This study is a phase II, open-label, multicenter clinical trial designed to evaluate two different treatment options for patients with metastatic colorectal cancer whose disease has progressed after standard therapies. The study compares a rechallenge treatment using irinotecan plus cetuximab with the current standard of care, trifluridine/tipiracil plus bevacizumab, as third-line therapy. Patients enrolled in the study are selected based on specific molecular characteristics of their cancer, identified through circulating tumor DNA analysis from a blood sample. The main purpose of the study is to determine whether the rechallenge with irinotecan and cetuximab leads to a higher tumor response rate compared with trifluridine/tipiracil plus bevacizumab. Secondary objectives include evaluating progression-free survival, overall survival, safety, and quality of life. Patients will be randomly assigned to one of the two treatment groups and will receive treatment until disease progression, unacceptable side effects, or withdrawal of consent. Tumor response will be assessed using standard imaging techniques according to RECIST criteria.
Male or female aged ≥18 years
Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1
Diagnosis of histologically or cytologically confirmed colorectal cancer.
At least one measurable lesion according to RECIST1.1
ECOG PS ≥2
Received more than 2 lines of treatment for metastatic disease.
Previous treatment with trifluridine/tipiracil
RAS/BRAF/EGFR/PIK3CAex20/MAP2K1/MET WT HER2 not amplified status at liquid biopsy analysis during screening.