CAPRI-3 GOIM Study: Phase 3 Clinical Study to Evaluate the Use of Continuing Cetuximab Treatment Beyond First Line Progression in Molecular Selected Metastatic Colorectal Cancer Patients.
The goal of this Phase 3 clinical trial is to evaluate whether continuing cetuximab treatment beyond first-line progression can improve outcomes in patients with metastatic colorectal cancer whose tumors are RAS and BRAF wild-type. The study will compare the effectiveness of chemotherapy given together with cetuximab versus chemotherapy given together with bevacizumab. Researchers aim to determine whether cetuximab continuation improves tumor response, progression-free survival, overall survival, and safety in this patient population. Eligible participants are adults with metastatic colorectal cancer who have previously responded to first-line treatment with chemotherapy combined with an anti-EGFR antibody. Before starting therapy, patients will undergo molecular testing using liquid biopsy to confirm tumor characteristics. They will then receive chemotherapy with either cetuximab or bevacizumab every two weeks, and their disease will be monitored regularly with CT or MRI scans, laboratory tests, and clinical evaluations. During the study, patients will also provide biological samples for translational research. This trial will enroll about 360 patients across sites in Italy and Spain and is designed to provide new evidence on whether cetuximab continuation beyond first-line treatment can offer a meaningful clinical benefit compared with standard therapy.
• Histologically proven diagnosis of colorectal adenocarcinoma.
• Diagnosis of metastatic disease.
• Efficacy of a first line therapy containing anti-EGFR drug with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1) or a prolonged (at least 6 months) stable disease.
• Progression to first line therapy.
• RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis.
• RAS (NRAS and KRAS exon 2,3 and 4), BRAFV600E, PIK3CA, EGFR ECD wild-type and HER2 not amplified in liquid biopsy at the time of screening (according to NGS, Foundation/Roche).
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1).
• Male or female patients ≥ 18 years of age.
• ECOG Performance Status 0-1.
⁃ Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment as defined by the following parameters:
⁃ Bone marrow:
‣ Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
‣ Hemoglobin (Hgb) ≥ 9 g/dL
‣ Platelets ≥ 100 x 109/L
⁃ Liver function:
⁃ • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and ALT (SGPT) ≤ 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN
⁃ Renal function:
⁃ • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
⁃ If female and of childbearing potential\*, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.
⁃ \*A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
⁃ If female and of childbearing potential, or if male, agreement to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 6 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.
⁃ Signed informed consent obtained before screening.