A Prospective Study of Levoleucovorin/5-FU Co-Infusion Combined With Liposomal Irinotecan ±Cetuximab/Bevacizumab as Second-Line Therapy for MSS Metastatic Colorectal Cancer
This is a single-center, single-arm study designed to evaluate the efficacy and safety of second-line treatment in patients with advanced colorectal cancer (those who have progressed on or are intolerant to first-line oxaliplatin-based regimens with or without targeted therapy) receiving Levofolinic Acid + 5-FU continuous infusion combined with irinotecan hydrochloride liposome ± cetuximab/bevacizumab. Approximately 30 patients will be enrolled.
• Male or female, aged 18-75 years.
• Histologically or cytologically confirmed colorectal adenocarcinoma.
• Unresectable, MSS-type metastatic colorectal cancer that has failed or is intolerant to first-line standard oxaliplatin plus fluoropyrimidine ± targeted therapy.
‣ Failure definition: progression during or within 3 months after completing first-line oxaliplatin/fluoropyrimidine ± targeted therapy.
⁃ Adjuvant setting: progression/recurrence during or within 6 months of completing adjuvant oxaliplatin-based chemotherapy/chemoradiation counts as first-line failure.
• At least one measurable lesion by RECIST 1.1.
• ECOG performance status 0-1.
• Expected survival ≥ 3 months.
• Adequate organ function within 14 days before enrollment (no transfusion or growth-factor support):
‣ Hematology: Hb ≥ 90 g/L; WBC ≥ 3.0 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; PLT ≥ 90 × 10⁹/L.
⁃ Coagulation: INR ≤ 1.5 × ULN; APTT ≤ 1.5 × ULN (stable anticoagulation at therapeutic range allowed).
⁃ Renal: Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault).
⁃ Hepatic:
⁃ No liver mets: TBIL ≤ 1.5 × ULN, ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN.
⁃ Liver mets: TBIL ≤ 2 × ULN, ALT ≤ 5 × ULN, AST ≤ 5 × ULN.
⁃ Cardiac: LVEF ≥ 50 %.
• Voluntary written informed consent; willing and able to comply with study procedures and follow-up.
• WOCBP must have a negative serum/urine pregnancy test within 3 days before first study-dose (Cycle 1 Day 1).
⁃ All subjects (men and women) with reproductive potential must use a highly effective contraceptive method (annual failure rate \< 1 %) from screening until 120 days after the last dose of investigational product or 180 days after the last chemotherapy dose, whichever is later.