Liposomal Irinotecan (II) Fractionated Dosing Combined With 5-FU/LV (FOLFIRInali-3) and Bevacizumab in Second-line Treatment of Advanced Colorectal Cancer: A Single-arm, Phase II Clinical Study

Prior treatment

• Participation in other drug trials within 4 weeks prior to enrollment;
• Concomitant use of strong CYP3A4/CYP2C8 inhibitors/inducers or UGT1A1 inhibitors within 2 weeks;

Other illness

• History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
• Uncontrolled hypertension (SBP \>160 mmHg or DBP \>100 mmHg);
• Acute coronary syndrome (including MI/unstable angina) with coronary angioplasty/stent placement within 6 months;
• NYHA class II+ heart failure, unstable angina, MI, or severe arrhythmia with cardiovascular impairment within 6 months;
• Severe comorbidities requiring hospitalization (e.g., ileus, bowel obstruction, pulmonary fibrosis, refractory diabetes, heart/kidney/liver failure, psychiatric/cerebrovascular disorders);
• Gastrointestinal perforation/fistula, intra-abdominal abscess, or non-GI fistula within 6 months;

Other

• Symptomatic brain metastases;
• Pregnancy or lactation;
• Other investigator-determined contraindications.

• Signed the informed consent；
• Male or female patients ≥18 years old;
• ECOG physical status score is 0 or 1;
• Patients with pathologically confirmed advanced colorectal carcinoma (all other histological types excluded);
• Patients who experienced disease progression under either of the following circumstances:During or within 6 months after first-line oxaliplatin-containing chemotherapy, or within 1 year after completing oxaliplatin-based adjuvant chemotherapy post-resection;
• Expected survival time ≥ 3 months;
• Patients must have at least one measurable metastatic lesion according to RECIST version 1.1;
• Normal organ function:
  • Hematology :Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3); Platelet count ≥ 100 × 109/L (100000/mm3); Hemoglobin ≥ 90g/L;
  • Kidney:The calculated value of creatinine clearance rate (CrCl) is ≥ 50 mL/min; Normal urine routine, urine protein\<2+or 24-hour (h) urine protein quantification\<1.0 g;
  • Liver:Total serum bilirubin (TBiL) ≤ 1.5 × ULN;AST and ALT ≤ 2.5 × ULN; For subjects with liver metastasis, AST and ALT can be ≤ 5 × ULN;Serum albumin (ALB) ≥ 30g/L;
  • Normal coagulation function, international standardized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
• Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; For males, surgical sterilization or agreement to use appropriate methods of contraception during observation and within 8 weeks after the last administration of study medication should be considered;
• Comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study;