Phase I/II Clinical Study of Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) Combined With Immunotherapy and Chemotherapy in Patients With Cholangiocarcinoma
The primary objective of this study is to evaluate the efficacy and safety of PULSAR in combination with dual immune checkpoint inhibitors (PD-1 monoclonal antibody + CTLA-4 monoclonal antibody) and GC chemotherapy in patients with locally advanced or metastatic cholangiocarcinoma. The secondary objective of this study is to investigate the immunological impact of PULSAR combined with dual immune therapy (PD-1 monoclonal antibody + CTLA-4 monoclonal antibody) on the tumor microenvironment and systemic immune responses in cholangiocarcinoma patients.
• Signed informed consent. The subject has fully understood and accepted the purpose, content, expected efficacy, mechanism of action, and risks of the study, and has signed the informed consent form.
• Age 18-75 years, regardless of gender.
• Histopathologically or cytologically confirmed locally advanced or metastatic cholangiocarcinoma.
• At least one measurable lesion based on RECIST 1.1 criteria.
• ECOG performance status score of 0-1.
• Expected survival time ≥3 months.
• Willing to comply with study procedures and able to undergo treatment (including radiotherapy, immunotherapy, chemotherapy) and follow-up.
• No contraindications to the use of PD-1, PD-L1 inhibitors, gemcitabine, or cisplatin.
• No contraindications to radiotherapy.
⁃ Organ function levels meet the following requirements: - Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; - Platelet (PLT) count ≥ 80 × 10⁹/L; - Hemoglobin (Hb) level ≥ 90 g/L; - Total bilirubin (TBil) level ≤ 1.5 times the upper limit of normal (ULN); - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN; if liver metastases are present, ≤ 5 times ULN; - Serum creatinine ≤ 1.5 times ULN, or calculated creatinine clearance rate ≥ 50 ml/min; - International normalized ratio (INR) ≤ 1.5 times ULN, and prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN, unless the subject is receiving anticoagulant therapy. - Hepatitis B surface antigen (HBsAg) positive with peripheral blood hepatitis B virus DNA (HBV-DNA) titer ≤ 1 × 10³ copies/L; if HBsAg positive and peripheral blood HBV-DNA titer ≥ 1 × 10³ copies/L, subjects may be included if the investigator determines that the chronic hepatitis B is stable and poses no additional risk.
⁃ Women of childbearing potential must agree to use appropriate contraceptive measures during the study period. Additionally, a serum or urine pregnancy test performed within 24 hours prior to the initiation of chemotherapy must be negative.
⁃ Women must be non-lactating.