Histologically confirmed advanced hepatocellular carcinoma or biliary tract malignancies (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) that have failed at least one line of prior systemic therapy
Conditions
Interventions
Trial group:Spatial fractionated radiotherapy (SFRT) for selected large tumors
concurrent Tislelizumab and anti-angiogenic targeted therapy within 1 to 7 days after completion of grid radiotherapy
anti-angiogenic targeted drugs include Lenvatinib, Regorafenib, Anlotinib, and Sunitinib (selected by investigators based on prior treatment history). First efficacy assessment at 4 weeks after SFRT c
Sponsors
Peking University International Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent prior to enrollment. 2. Age >18 years, male or female. 3. Histologically or pathologically confirmed advanced hepatocellular carcinoma or biliary tract malignancies (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer). 4. Progression or intolerance after prior systemic therapy. 5. Presence of measurable lesions outside the radiotherapy field (RECIST 1.1 criteria). 6. Presence of a lesion with a short diameter >=5 cm assessed by the investigator as suitable for spatially fractionated radiotherapy (SFRT). 7. ECOG performance status score: 0-2. 8. Life expectancy >12 weeks. 9. Routine laboratory tests meeting the following requirements (without any blood product or cell growth factor transfusion within 14 days): (1) Complete blood count: neutrophil count >=1.5x10^9/L; platelet count >=75x10^9/L; hemoglobin >=80 g/L. (2) Liver and kidney function: serum creatinine (SCr) =50 mL/min (Cockcroft Gault formula); total bilirubin (TBIL) =2+, then 24 hour urine protein quantification shows protein <=1 g. 10. Normal coagulation function, no active bleeding or thromboembolic disease: (1) International normalized ratio (INR) <=1.5xULN. (2) Activated partial thromboplastin time (APTT) <=1.5xULN. (3) Prothrombin time (PT) <=1.5xULN. 11. For female patients of childbearing potential (non surgically sterilized): must agree to use a medically approved contraceptive method (e.g., intrauterine device, oral contraceptive, or condom) during the study treatment period and for 3 months after the end of treatment; have a negative serum or urine HCG test within 7 days prior to enrollment; and must not be breastfeeding. For male patients (non surgically sterilized or of childbearing potential): must agree to use a medically approved contraceptive method with their partner during the study treatment period and for 3 months after the end of treatment. 12. Subjects voluntarily participate in this study, have good compliance, and cooperate with safety and survival follow up.
Exclusion criteria
Exclusion criteria: 1.The subject has a prior or concurrent other malignancy (except for cured cutaneous basal cell carcinoma and cervical carcinoma in situ). 2. Known history of allergy to macromolecular protein preparations or to any component of the study drugs. 3. The subject has any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects who have undergone thyroid surgery cannot be enrolled). Subjects with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be enrolled. Subjects requiring bronchodilators for medical intervention for asthma cannot be enrolled. 4. The subject is receiving immunosuppressive agents or systemic corticosteroid therapy for immunosuppressive purposes (dose >10 mg/day prednisone or equivalent), and this therapy is ongoing within 4 weeks prior to enrollment. 5. Presence of poorly controlled cardiac clinical symptoms or diseases, such as: (1) heart failure of NYHA class =2; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention. 6. The subject has an active infection or unexplained fever >38.5°C during the screening period or before the first dose (subjects with fever due to tumor may be enrolled at the investigator's discretion). 7. Past or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired lung function. 8. The subject has congenital or acquired immunodeficiency, such as HIV infection. 9. Receipt of live vaccine within less than 4 weeks prior to study drug administration or potential receipt of live vaccine during the study period. 10. The subject has a known history of substance abuse, alcohol abuse, or drug addiction. 11. Patients unable to take oral medication. 12. Receipt of Chinese herbal medicine or traditional Chinese patent medicine with anti tumor indications within 2 weeks prior to the first dose. 13. The investigator judges that the subject should be excluded from this study, for example, the presence of other factors that may lead to premature termination of the study, such as other serious diseases (including psychiatric disorders) requiring concomitant treatment, severe gastric/esophageal varices, serious laboratory abnormalities, or family/social factors that may affect the subject's safety or the collection of data and samples.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Local Control Rate in Large Tumors Receiving SFRT;Abscopal Response Rate;Overall Disease Control Rate;Objective Response Rate;Overall Survival; | — |
Countries
China
Contacts
Public ContactLi Li
Peking University International Hospital
Outcome results
None listed