Irinotecan liposome combined with 5-FU/LV has shown good efficacy and has certain advantages in reducing the adverse reactions of conventional chemotherapy drugs. Adjuvant treatment of high-risk factors after surgery for biliary tract tumors can be further explored and attempted. Therefore, this study intends to conduct an exploratory study comparing oral capecitabine with irinotecan liposome +5-FU/LV for adjuvant therapy in high-risk patients after resection of resectable biliary malignancies, and evaluate the effectiveness and safety of irinotecan liposome +5-FU/LV as adjuvant therapy for high-risk patients after resection of resectable biliary malignancies. So it can provide more treatment options for patients with postoperative adjuvant therapy of biliary tract malignant tumor.

The DFS rate one year after surgery for biliary malignancy was assumed to be 51.4% with a maximum response rate of poor efficacy and 71.4% with a minimum response rate of good efficacy. A two-stage design was adopted with α=0.05 and certainty (1-β) =0.8, and Minimax was adopted. If a response occurs in 7 out of 14 patients or less, treatment options are rejected; In the second phase, if 24 or fewer responses occur in 38 patients, the protocol is rejected. A total of 38 samples were designed in two stages. The 1-year DFS rate was at least 65.8% in the total population of the test and control groups.

According to the 2023 CSCO guidelines, differentiated surgical treatment has been performed for the site of biliary malignancies. For postoperative adjuvant therapy, BILCAP study showed that oral capecitabine as a single drug is one of the options for both efficacy and safety. For patients with postoperative risk factors, serum carcinoembryonic antigen (CEA) and CA19-9 are of some significance for monitoring recurrence, and often serve as precursors for clinical judgment of recurrence or progression. For people with high risk factors for recurrence and progression, adjuvant therapy intensity needs to be strengthened. Oral capecitabine can no longer meet the needs of this population, so patients need to be given intravenous chemotherapy in advance to control progression, recurrence or metastasis. In this case, metastatic first-line therapy is often used for early intervention. The NIFE study showed that compared with conventional chemotherapy regimens, the regimen of irinotecan liposome (new formulation) combined with 5-FU/LV achieved relatively better efficacy data in the median OS and ORR efficacy. It is noteworthy that this regimen has a significant therapeutic benefit in patients with advanced first-line extrahepatic cholangiocarcinoma, with a median PFS of 9.59 months and a median OS of 18.23 months.

To explore the efficacy and safety of irinotecan liposomes +5-FU/LV versus oral capecitabine in patients at high risk of recurrence after resection of resectable biliary malignancies.

Inclusion Criteria:

• Age 18-75 years old.
• Patients with histologically confirmed, resectable biliary malignancies with R0 resection.
• Postoperative pathology indicated the following risk factors: positive lymph nodes, vascular invasion, nerve invasion and so on.
• Has not received systemic chemotherapy before.
• The ECOG score is 0 to 1.
• Bone marrow and organ function were good: ① Neutrophils (ANC) ≥1.5×109/L, platelets (PLT) ≥100×109/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×109/L, albumin (ALB) ≥32 g/L, and no bleeding tendency; ② Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤2.5× upper limit of normal range (ULN), ≤5×ULN with liver metastasis; Total bilirubin ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 mL/min (calculated according to Cockroft-Gault).
• Expected survival ≥3 months.
• Volunteer to participate in the study and sign the informed consent. If the subject does not have the ability to read the informed consent (e.g., illiterate subjects), a witness must witness the informed process and sign the informed consent.

Exclusion Criteria:

• Patients allergic to the investigational drug and its excipients.
• Known or suspected central nervous system or lymphatic metastasis.
• Cannot discontinue use or has not discontinued use of CYP3A, CYP2C8, and UGT1A1 potent depressants or inducers (e.g., anticonvulsants [phenytoin, phenobarbital, or carbamazepine] within 2 weeks prior to enrollment), rifampicin, rifambutin, St.John's Wort, Grapefruit juice, clarithromycin, Itraconazole, Lopinavir, Nefazodone, Nelfinavir, Ritonavir, Saquinavir, Terrapivir, voriconazole, Azanavir, Gefilozil, Indinavir, etc.).
• There are signs and symptoms of intestinal obstruction.
• Other malignancies within the past 5 years or currently, except for cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancers.
• Autoimmune disease or long-term steroid use.
• Patients who are pregnant or nursing women, and patients who refuse to receive contraception during their reproductive age.
• Patients deemed unsuitable for participation in this study.
• Vulnerable groups, including people with mental illness, cognitive impairment, critically ill patients, etc.

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