Table 1 Inclusion criteria
- Have histological or cytological documentation of adenocarcinoma of the colon or rectum. | |
- Have synchronous or metachronous metastatic colorectal cancer not amenable to surgical resection with curative intent and no prior therapy for metastatic disease. | |
- Have a tumor RAS mutation | |
- Have a wild-type homozygous or an heterozygous status of the UGT1A1 regarding UGT1A*28. | |
- Have a serum uracil < 16 ng/ml | |
- Have a measurable disease, according to RECIST version 1.1 | |
- Have signed written informed consent | |
- Be aged 18 or older | |
- Have an Eastern Cooperative Oncology Group performance status ≤1 and a life expectancy of at least 3 months. | |
- Have an adequate bone marrow, renal and liver functions as evidenced by the following laboratory requirements: absolute neutrophil count ≥1500/ mm3, platelet count ≥100,000/mm3, Hemoglobin ≥9 g/dL, serum creatinine ≤1.5 x upper limit of normal (ULN), serum calcium ≥ LLN and ≤ 1.2 x UNL; serum magnesium ≥ LLN and ≤ 1.2 x UNL; Kalemia ≥ LLN, glomerular filtration rate as assessed by the estimated glomerular filtration rate (eGFR) ≥ 50 mL/min per 1.73 m2 calculated by the Modification of Diet in Renal Disease (MDRD) abbreviated formula, total bilirubin ≤1.5 x ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement), alkaline phosphatase ≤2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement and/or bone metastases). | |
- Have serum lipase ≤1.5 x ULN. | |
- Have adequate coagulation, as assessed by the following laboratory test results: International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 x ULN, partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN. | |
- Have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test obtained within 7 days before the start of study treatment, in case of women with reproductive potential. For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 4 months following completion of therapy for women and 6 months for male patients. | |
- Must be able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. | |
- Must be affiliated to a French health insurance |