A Prospective, Single-Arm, Exploratory Clinical Study of Liposomal Irinotecan (II) Plus 5-Fluorouracil/Leucovorin and Sintilimab With Sequential Stereotactic Body Radiation Therapy as First-Line Treatment for Locally Advanced Biliary Tract Cancer
This is a prospective, single-arm, exploratory interventional study designed to evaluate the efficacy and safety of liposomal irinotecan (II) plus fluorouracil/leucovorin (5-FU/LV) and sintilimab with sequential stereotactic body radiation therapy (SBRT) as first-line treatment for patients with unresectable locally advanced biliary tract cancer (BTC) who have not received prior systemic anticancer therapy for their current disease. Approximately 31 participants will be enrolled. Participants will receive liposomal irinotecan (II), 5-FU/LV, and sintilimab. Participants without disease progression after initial systemic treatment will receive sequential SBRT to the primary biliary tract tumor. After eight administrations of chemotherapy (approximately 16 weeks), resectability will be assessed by a multidisciplinary team. Participants considered eligible for surgery will undergo radical surgical resection followed by adjuvant treatment, whereas those who remain unresectable will continue the study treatment until disease progression or another protocol-defined reason for discontinuation. The primary endpoint is objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), surgical conversion rate (SCR), and safety.
• Aged 18 to 80 years, inclusive, at the time of signing the informed consent form, regardless of sex.
• Histologically and/or cytologically confirmed biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
• Unresectable locally advanced disease at the current disease stage, as determined by a multidisciplinary team (MDT).
• No prior anticancer treatment for biliary tract cancer at the current disease stage, including radiotherapy, chemotherapy, immunotherapy, or biologic therapy.
• At least one measurable lesion according to RECIST version 1.1. The measurable lesion must not have received prior radiotherapy or other local treatment.
• Expected survival of at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, hepatic, renal, cardiac, and coagulation function within 14 days before initiation of study treatment, meeting all of the following requirements:
‣ Hematologic function: absolute neutrophil count (ANC) ≥1.5 × 10\^9/L; platelet count ≥100 × 10\^9/L; hemoglobin ≥90 g/L (9.0 g/dL); and no blood transfusion or hematopoietic growth factor support for correction within 14 days before screening.
⁃ Biochemical function: serum albumin ≥30 g/L (3.0 g/dL); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × the upper limit of normal (ULN); total bilirubin ≤1.5 × ULN; and serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min as calculated using the Cockcroft-Gault formula.
⁃ Cardiac function: normal 12-lead electrocardiogram or abnormalities considered clinically insignificant by the investigator, with QTcF \<470 ms; and left ventricular ejection fraction (LVEF) ≥50%.
⁃ Coagulation function: prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 × ULN and international normalized ratio (INR) ≤1.5 × ULN in participants not receiving anticoagulant therapy. Participants receiving a stable dose of anticoagulant therapy, such as low-molecular-weight heparin or warfarin, may be eligible if the INR is within the expected therapeutic range.
• Willing to participate voluntarily, provide written informed consent, and comply with scheduled study visits and other protocol requirements.