Regorafenib as Second-line Treatment of Patients With RAS-mutant Advanced Colorectal Cancer: a Multicentre, Phase 2 Study
The investigators hypothesize that patients with mCRC RAS-mutant eligible for a second line treatment with good prognostic features, identified as single metastatic site, long progression free survival (PFS) in first line treatment, might benefit from a personalized approach, with less intensive treatment with regorafenib as part of a continuum-of-care strategy aimed at ensuring quality of life and extending survival.
• Written informed consent to study procedures and to correlative studies.
• Either sex aged ≥ 18.
• Histologically proven of colorectal adenocarcinoma.
• Diagnosis of metastatic disease.
• RAS mutant at initial diagnosis assessed at local centers according with a validated method defined by EMA and known MMR/MSI status.
• Achieved a PFS in first line \> 6 months with chemotherapy in combination to antiangiogenic treatment OR with one metastatic site at study entry
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry.
• Imaging-documented measurable disease, according to RECIST 1.1 criteria.
• Estimated life expectancy of more than 12 weeks
⁃ Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL.
⁃ Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN.
⁃ Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula).
⁃ Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range.
⁃ Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory.