Overview

This is a multi-center, single-arm study to investigate the efficacy and safety of liposomal irinotecan+5-FU/LV+ bevacizumab as second-line therapy in metastatic colorectal cancer in Chinese population.

Eligibility

Inclusion Criteria:

• Age: 18-75 years old.
• Histologically or cytologically proven colon or rectum adenocarcinoma.
• Confirmed as unresectable metastatic disease through radiological examination.
• At least one measurable lesion (according to RECIST v1.1).
• First-line treatment with oxaliplatin-based therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 2.
• The expected survival time ≥3 months.
• Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10\^9/L.
• Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present.
• Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria \<2+.
• Normal coagulation function (INR≤1.5).
• Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.

Exclusion Criteria:

• Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
• Previous treatment with irinotecan/liposomal irinotecan.
• MSI-H/dMMR
• Massive pleural effusion or ascites requiring intervention.
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
• Active HIV, HBV, HCV infection.
• Combined with uncontrollable systemic diseases.
• Presence of severe gastrointestinal disease (including active bleeding, \> grade 1 obstruction , \> grade 1 diarrhea or gastrointestinal perforation)
• History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment.
• Presence of interstitial pneumonia or pulmonary fibrosis.
• Allergy to or intolerance to therapeutic drugs or their excipients;.
• History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment.
• Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment.
• Patients with symptomatic central nervous system metastases.
• Documented serum albumin ≤3 g/dL
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
• Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
• Participated in other trial within 30 days prior to the first dose of study treatment.
• Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug
• Patients who are not suitable to participate in this trial for any reason judged by the investigator.