Prospective, Single-arm, Single-center Phase Ib/II Trial on the Safety and Efficacy of Fruquintinib in Combination With FOLFIRI in RAS-mutated Metastatic Colorectal Cancer
Molecular subtypes make difference on clinicopathologic features and response to chemotherapy and targeted agents as well as prognosis. RAS mutation status, which accounting for approximately 35% to 40% of colorectal cancer patients, is an important factor considered in the standard of care for colorectal cancer. For RAS-mutated patients, no targeted driver gene drugs have been approved, and their treatment is based on the anti-VEGF/VEGFR pathway, and corresponding targeted drugs such as bevacizumab, aflibercept, and ramucirumab have also been successfully marketed for the treatment of CRC. For RAS mutant metastatic colorectal cancer, the commonly used first-line treatment regimen is bevacizumab combined with chemotherapy, which is shown in previous studiesthat the PFS of 1st-line is about 10 months; the standard regimen of second-line treatment is FOLFIRI ± bevacizumab, which is shown in previous study that the 2nd-line PFS is about 5 months with ORR 4%. There are a lot of unmet medical needs to improve the clinical efficacy in secondline-treatment of RAS-mutant patients.
• Fully understand the study and voluntarily sign the informed consent form;
• Age ≥ 18 years;
• Pathologically confirmed unresectable metastatic colorectal cancer;
• Known RAS gene mutations;
• failed standard first-line FOLFOX/XELOX combined with bevacizumab;
• ECOG performance status 0-1;
• BMI ≥ 18;
• Expected survival ≥ 3 months;
• Vital organ function meets the following requirements (any blood components and cell growth factors are not allowed within 14 days before enrollment):
‣ Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L;
⁃ Platelets ≥ 100 x 109/L;
⁃ Hemoglobin ≥ 90 g/L;
⁃ Total bilirubin TBIL ≤ 1.5 × ULN;
⁃ ALT and AST ≤ 5 x ULN;
⁃ Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 x ULN (and creatinine clearance (CCr) ≥ 50 mL/min);
⁃ Left ventricular ejection fraction (LVEF) \> = 50%;
⁃ Fridericia corrected QT interval (QTcF) \< 470 milliseconds.
⁃ INR ≤ 1.5 x ULN, APTT ≤ 1.5 x ULN.
⁃ Women of childbearing age should take effective contraceptive measures;
⁃ Good compliance and cooperation with follow-up.