Phase II Study of Irinotecan Liposomes in First-line Treatment of Metastatic Colorectal Cancer

Inclusion Criteria:

• 18~85 years old.

• Histopathologically confirmed patient with an inoperable metastatic colorectaladenocarcinoma.

• RAS/BRAF v600e mutant or right half colon cancer is known.

• pMMR/MSS is known.

• The unresectable stage of metastatic disease has not received any systemic antitumortherapy.

• For subjects previously receiving neoadjuvant or adjuvant therapy, the date of firstdiscovery of disease progression must be at least 6 months removed from the date oflast administration of neoadjuvant or adjuvant therapy.

• ECOG 0~1, patients ≥75 years old need an ECOG score of 0

• The presence of at least 1 measurable lesion that can be evaluated according to theRECIST v1.1 criteria.

• Normal bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×10^9/L, platelets (PLT) ≥100×10^9/L, hemoglobin (Hb) ≥80g/L, albumin (ALB) ≥30 g/L, white blood cells (WBC) ≥3.0×10^9/L, and no bleeding tendency; ② AST, ALT and alkaline phosphatase (ALP) were all ≤2.5× upper limit of normal range (ULN), and ≤5×ULN when livermetastases occurred; The total bilirubin level doesn't exceed the upper limit of theagency's normal range; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥40ml/min (calculated according to Cockroft-Gault)

• Understand the situation of this study, patients and/or legal representativesvoluntarily agree to participate in this study and sign informed consent form.

Exclusion Criteria:

• Known or suspected central nervous system metastasis.

• Received irinotecan/irinotecan liposomes/bevacizumab before enrollment.

• Had undergone surgery and other oncologic treatments within the first 4 weeks ofenrollment.

• Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 I orbelow(except hair loss and peripheral neuropathy).

• The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinuedor were not discontinued within 2 weeks prior to enrollment.

• Severe gastrointestinal dysfunction, gastrointestinal perforation, intraperitonealabscess, and fistula.

• Intestinal obstruction, signs and symptoms of intestinal obstruction, or the stenthas been previously implanted and the stent has not been removed before thescreening period.

• Interstitial lung disease.

• Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding).

• Patients with fluid accumulation that couldn't reach a stable state but small amountof ascites on imaging without clinical symptoms could be enrolled.

• Any serious or uncontrolled systemic disease, including uncontrolled high bloodpressure, heart disease, active bleeding, active viral infection, etc.

• Have had other malignancies within the past 5 years or currently, except curedcervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer.

• Patients of childbearing age who refuse to take contraceptives, women who arepregnant or breastfeeding.

• The researchers didn't consider it appropriate to participate in this study.