Phase III Study in mCRC Patients With RAS/BRAF Wild Type Tissue and RAS Mutated in LIquid BIopsy to Compare in First-line Therapy FOLFIRI Plus CetuxiMAb or BevacizumaB (LIBImAb Study)
This study is a prospective, randomized phase III, to evaluate if in patients with mCRC RAS/BRAF wild type on tumor tissue and RAS mutations on liquid biopsy, treating in first line with antibody anti-VEGF (bevacizumab) plus chemotherapy (FOLFIRI) is superior in terms of PFS compared to standard treatment with antibody anti-EGFR (cetuximab) plus FOLFIRI, and then in patients RAS/BRAF wild type on tumor tissue who develop RAS mutations on liquid biopsy after the beginning of the first line treatment with cetuximab plus FOLFIRI, in the absence of a clinical or radiological progression disease, to anticipate a change of treatment with bevacizumab plus FOLFIRI further impacts on the PFS.
• Provision of written informed consent;
• Male or female \> 18 years of age;
• Histologically confirmed diagnosis of colorectal adenocarcinoma RAS/BRAF wild type (analysed either on primary and/or related metastasis);
• Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
• Patient with left colorectal cancer;
• Patients suitable for first line chemotherapy;
• Life expectancy \> 3 months;
• At least one site of measurable disease per RECIST criteria ver. 1.1;
• ECOG Performance status = 2;
⁃ Adequate bone marrow, liver and renal function assessed before starting study treatment;
⁃ If DPD status is known it must be wild type. No restrictions are applied if DPD status in unknown;
⁃ Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study treatment. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
⁃ Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception).