unresectable hepatocellular carcinoma
Conditions
Interventions
Test group:Gecacitinib, donafenib, and tislelizumab
Sponsors
Chongqing University Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily agrees to participate in the study and signs the written informed consent form; 2. Aged 18 to 80 years, inclusive, male or female; 3. Patients with hepatocellular carcinoma clinically diagnosed according to the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition), or confirmed by histology/cytology; 4. Patients with unresectable hepatocellular carcinoma who have not previously received systemic therapy; 5. Patients who have received no more than one prior TACE/HAIC treatment; 6. Patients who have previously received HIFU, ablation, or radiotherapy are allowed to be enrolled; 7. At least one evaluable lesion according to RECIST v1.1; 8. Expected survival time of =3 months; 9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0–1; 10. Child-Pugh score of <=7; 11. Able to cooperate with the observation of adverse events and efficacy; 12. Patients positive for HBcAb are allowed to be enrolled; patients positive for HBsAg should continue antiviral therapy with first-line antiviral agents such as entecavir, tenofovir, or tenofovir alafenamide fumarate; 13. Adequate major organ function.
Exclusion criteria
Exclusion criteria: 1. Histologically/cytologically confirmed hepatocellular carcinoma with components such as fibrolamellar HCC, sarcomatoid HCC, or cholangiocarcinoma; 2. History of malignancies other than hepatocellular carcinoma, unless the following criteria are met: a. The patient has received potentially curative treatment and has had no evidence of the disease within the past 5 years; b. Successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other carcinoma in situ; 3. Diffuse tumor lesions; 4. History of hepatic encephalopathy, hepatorenal syndrome, or liver transplantation; 5. Pleural effusion, ascites, or pericardial effusion with clinical symptoms requiring drainage; 6. Central nervous system metastases; 7. Previous history of severe psychiatric illness; 8. Diseases affecting the absorption, distribution, metabolism, or elimination of the study drugs, such as severe vomiting, chronic diarrhea, intestinal obstruction, or malabsorption. 9. Prior allogeneic stem cell transplantation or solid organ transplantation; 10. Concomitant use of drugs that may prolong QTc and/or induce torsades de pointes (TdP), or drugs that affect drug metabolism; 11. Previous or current congenital or acquired immunodeficiency disease; 12. Active or documented history of autoimmune disease or inflammatory disease, including but not limited to autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism or hypothyroidism, or asthma requiring bronchodilator therapy. Patients with vitiligo or asthma that completely resolved during childhood and requires no intervention in adulthood may be enrolled. 13. Known or suspected history of allergy to JAK inhibitors, donafenib, or similar drugs; history of hypersensitivity to chimeric or humanized antibodies; or allergy to any excipient of the study drugs; 14. Active bleeding or coagulation abnormalities, bleeding tendency, or current treatment with thrombolytic, anticoagulant, or antiplatelet therapy; 15.Thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, or pulmonary embolism; 16. Esophageal or gastric variceal bleeding caused by portal hypertension within the past 6 months, or any life-threatening bleeding event within the past 3 months; 17. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within the past 6 months; congestive heart failure (New York Heart Association [NYHA] class > II); poorly controlled arrhythmia or arrhythmia requiring pacemaker therapy; or hypertension not controlled by medication, defined as systolic blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg; 18. Other clinically significant clinical or laboratory abnormalities that, in the investigator’s opinion, may affect safety evaluation, such as uncontrolled diabetes mellitus, chronic kidney disease, grade II or higher peripheral neuropathy according to CTCAE v5.0, or thyroid dysfunction; 19. Severe infection that is active or poorly controlled clinically; active infections, including: a. Positive human immunodeficiency virus (HIV) test (HIV-1/2 antibodies); b. Active hepatitis B, defined as HBsAg positive with HBV DNA positive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate(ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| 12-week Objective Response Rate(12-week ORR);6-month Progression-Free Survival rate;Progression-Free Survival(PFS);1-year Overall Survival rate;Disease Control Rate (DCR);Incidence of Adverse Events;Duration of Response(DOR); | — |
Countries
China
Contacts
Public ContactLi Yongsheng
Chongqing University Cancer Hospital
Outcome results
None listed