Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Regorafenib as First-Line Therapy for Advanced Cholangiocarcinoma

Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Regorafenib as First-Line Therapy for Advanced Cholangiocarcinoma: A Single-Centre, Single-Arm, Phase II Trial

The goal of this clinical trial is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with tislelizumab and regorafenib as first-line therapy in patients with locally advanced or metastatic cholangiocarcinoma.

The main questions it aims to answer are:

1. What is the objective response rate (ORR) of this combination regimen according to RECIST 1.1 criteria
2. What are the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile associated with this treatment

Participants will:Receive hepatic arterial infusion chemotherapy (HAIC)+ tislelizumab (PD-1 inhibitor)+regorafenib (oral multikinase inhibitor). Undergo regular imaging assessments to evaluate tumor response per RECIST 1.1.Be monitored for survival outcomes and adverse events throughout treatment and follow-up.

Inclusion Criteria:

1. Age 18-75 years ;
2. Histologically or cytologically confirmed unresectable locally advanced or metastatic intra- or extrahepatic cholangiocarcinoma ;
3. Clinical stage III-IV according to the 8th edition of the AJCC TNM classification ;
4. No prior antitumor therapy;
5. Child-Pugh liver function class A or B ;
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
7. At least one measurable lesion per RECIST 1.1 ;
8. Adequate haematologic and hepatic/renal function;
9. Total bilirubin ≤ 2× upper limit of normal (patients who have undergone biliary drainage are eligible) ;
10. Adequate cardiac and pulmonary reserves to tolerate interventional procedures ;
11. Signed informed consent, good compliance, and ability to attend follow-up visits.

Exclusion Criteria:

1. Contraindications to transarterial chemoembolization, targeted therapy, or immunotherapy ;
2. Prior antitumor treatment ;
3. Concurrent primary malignancies;
4. Child-Pugh class C;
5. Severe cardiac, pulmonary, or renal dysfunction ;
6. Active autoimmune disease or need for long-term immunosuppressive therapy ;
7. Hypersensitivity to contrast agents or study drugs ;
8. Pregnancy or lactation;
9. Anticoagulant or thrombolytic therapy within 3 months before enrollment or bleeding diathesis.