Biliary Cancer Metastatic
Conditions
Brief summary
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.
Interventions
DRUGBevacizumab+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.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) according to RECIST Version 1.1 | Every 6 weeks until disease progression, up to 24 months | Percentage of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival According to RECIST Version 1.1 | Up to 24 months | Time from first dose until disease progression according to RECIST version 1.1 or death. |
| Disease Control Rate (DCR) | Every 6 weeks from first dose until disease progression, up to 24 months | Percentage of participants achieving CR, PR or stable disease according to RECIST version 1.1. |
| Duration of Response (DoR) | Up to 24 months | Time from first documented response until disease progression or death. |
| Overall Survival (OS) | Up to 24 months | Time from enrollment to the patient's death for any cause |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From first dose through 90 days after last dose | Incidence and severity of treatment-emergent adverse events assessed according to CTCAE version 5.0. |
| Change From Baseline in EORTC QLQ-C30 Global Health Status Score | Baseline through 24 months | Quality of life assessed using the EORTC QLQ-C30 questionnaire. |
Countries
China
Outcome results
None listed