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

Efficacy and Safety of Bevacizumab With Nab-paclitaxel and Tegafur Gimeracil Oteracil Potassium Capsule (S-1) in Advanced Biliary Tract Adenocarcinoma

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.

Study Overview

• Status: Completed
• Conditions: Biliary Cancer Metastatic
• Intervention / Treatment: Drug: Bevacizumab+nab-paclitaxel+tegafur gimeracil oteracil potassium capsule (S-1)

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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) <500 IU/mL (or <2,500 copies/mL).
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Women of childbearing potential must use highly effective contraception during the study and for at least 120 days after the last dose of study treatment and must have a negative urine or serum pregnancy test within 7 days before the first dose of study treatment. Non-sterilized male participants must agree to use highly effective contraception during the study and for at least 120 days after the last dose of study treatment.

Exclusion Criteria:

• Histologically or cytologically confirmed fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma.
• Active autoimmune disease or a history of autoimmune disease with the potential for recurrence.
• Any condition requiring systemic treatment with corticosteroids at a dose of >10 mg/day of prednisone or equivalent, or other immunosuppressive agents, within 14 days before the first dose of study treatment.
• Inadequately controlled hypertension despite medical therapy, defined as systolic blood pressure >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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab plus nab-paclitaxel and tegafur gimeracil oteracil potassium capsule (S-1)	Drug: Bevacizumab+nab-paclitaxel+tegafur gimeracil oteracil potassium capsule (S-1); Patients received intravenous nab-paclitaxel at a dose of 125 mg/m2 on day 1 and 8, intravenous bevacizumab at a dose of 7.5 mg/kg on day 1, and oral S-1, 80 to 120 mg/day on days 1-14 of a 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) according to RECIST Version 1.1	Percentage of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST version 1.1.	Every 6 weeks until disease progression, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival According to RECIST Version 1.1	Time from first dose until disease progression according to RECIST version 1.1 or death.	Up to 24 months
Disease Control Rate (DCR)	Percentage of participants achieving CR, PR or stable disease according to RECIST version 1.1.	Every 6 weeks from first dose until disease progression, up to 24 months
Duration of Response (DoR)	Time from first documented response until disease progression or death.	Up to 24 months
Overall Survival (OS)	Time from enrollment to the patient's death for any cause	Up to 24 months
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Incidence and severity of treatment-emergent adverse events assessed according to CTCAE version 5.0.	From first dose through 90 days after last dose
Change From Baseline in EORTC QLQ-C30 Global Health Status Score	Quality of life assessed using the EORTC QLQ-C30 questionnaire.	Baseline through 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of predefined predictive biomarkers associated with treatment response	Assessment of predefined tumor and blood biomarkers associated with treatment response.	Every 6 weeks until disease progression, up to 24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2026
• Primary Completion (Actual): February 23, 2026
• Study Completion (Actual): February 23, 2026

Study Registration Dates

• First Submitted: July 13, 2026
• First Submitted That Met QC Criteria: July 19, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 19, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: S 1 (combination)
• Other Study ID Numbers: SH-202521

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No