Bevacizumab Plus Nab-paclitaxel and Tegafur Gimeracil Oteracil Potassium Capsule (S-1) as Second-line Treatment for Advanced Biliary Tract Cancer: a Phase Ⅱ Clinical Trial

This prospective, single-center, single-arm phase II clinical trial was designed to evaluate the efficacy and safety of bevacizumab plus nab-paclitaxel and S-1 as second-line treatment for patients with advanced biliary tract adenocarcinoma who experienced disease progression or intolerance after first-line systemic therapy. Participants received bevacizumab in combination with nab-paclitaxel and oral S-1 in 21-day treatment cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, or other protocol-defined discontinuation criteria. The primary outcome was objective response rate assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary outcomes included progression-free survival, disease control rate, duration of response, overall survival, quality of life, and safety. Exploratory analyses were conducted to investigate potential predictive biomarkers of treatment efficacy.

Inclusion Criteria: * Aged ≥18 years at the time of signing the informed consent form (ICF). * Histologically confirmed or clinically diagnosed biliary tract adenocarcinoma. * Unresectable disease and not suitable for locoregional therapy, or disease progression after locoregional therapy. * Child-Pugh class A or class B with a score of 7. * Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1. * Radiographic disease progression or intolerance after first-line treatment. * Adequate bone marrow, hepatic, and renal function, as defined by: 1. Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L, platelet count ≥75 × 10\^9/L, and hemoglobin ≥85 g/L; 2. Serum total bilirubin ≤1.5 × the upper limit of normal (ULN); 3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN; 4. Estimated glomerular filtration rate (eGFR) \>30 mL/min/1.73 m²; 5. International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN; 6. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. * For patients with hepatitis B virus (HBV) infection, HBV deoxyribonucleic acid (DNA) \140 mmHg or diastolic blood pressure \>90 mmHg. * Active gastrointestinal disorders, including active gastric or duodenal ulcer or ulcerative colitis; active bleeding from an unresected tumor; or any other condition considered by the investigator to pose a risk of gastrointestinal bleeding or perforation. Patients with a history of gastrointestinal perforation or gastrointestinal fistula that had not healed after surgical treatment were also excluded. * A history of arterial thrombosis or deep vein thrombosis within 6 months before enrollment, or evidence or a history of bleeding tendency within 2 months before enrollment, regardless of severity. * Any clinical or laboratory abnormality or compliance issue that, in the investigator's judgment, made the participant unsuitable for participation in the study.