Hepatocellular carcinoma
Conditions
Interventions
experimental group:Participants will first receive treatment with Jaktinib (100mg,Bid,po). After 7 consecutive days of medication, participants will begin treatment with Donafenib (100mg,Bid,po) and a
Sponsors
Yunnan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Voluntarily enroll and sign a written informed consent form; 2.Age 18 to 70 years (excluding 70 years), male or female; 3.Patients with hepatocellular carcinoma clinically diagnosed according to the Primary Liver Cancer Diagnosis and Treatment Guidelines (2024 Edition) or confirmed by histology/cytology; 4.Patients with unresectable hepatocellular carcinoma who have progressed after first-line treatment containing immune checkpoint inhibitors. Criteria for unresectability include: a.CNLC stage Ia-IIa: medically ineligible for surgical resection due to reasons such as ICg15 > 30%, future liver remnant (FLR) =3 months; 7.Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0–1; 8.Child-Pugh score = 7; 9. Ability to cooperate in observing adverse events and treatment efficacy; 10. For HBsAg-positive patients, continuous antiviral therapy with first-line antiviral agents such as entecavir, tenofovir, or tenofovir alafenamide fumarate is required; 11. Normal function of major organs, meeting the following criteria: Hematological tests (no transfusion or G-CSF use within 14 days prior to screening): a.Hemoglobin >= 90 g/L; b.Absolute neutrophil count (ANC) >= 1.5 × 10?/L; c.Platelet count >= 75 × 10?/L; Blood biochemistry tests (no albumin use within 14 days prior to screening): d. Albumin >= 28 g/L; e.Total bilirubin <= 2 × upper limit of normal (ULN); f.Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <= 5 × ULN; g. Alkaline phosphatase (ALP) <= 5 × ULN; h.Creatinine <= 1.5 × ULN; Coagulation function: i.International normalized ratio (INR) or prothrombin time (PT) <= 1.5 × ULN; j. Activated partial thromboplastin time (APTT) <= 1.5 × ULN.
Exclusion criteria
Exclusion criteria: Past or Concurrent Medical Conditions: 1.Previous histologically/cytologically confirmed components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc. 2.History of malignancies other than hepatocellular carcinoma, except under the following conditions: a.The patient has undergone potentially curative treatment and has had no evidence of the disease for 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 carcinomas in situ. 3.Diffuse tumor involvement. 4.History of hepatic encephalopathy, hepatorenal syndrome, or prior liver transplantation. 5.Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage. 6.Central nervous system metastases. 7.History of severe psychiatric disorders. 8.Diseases affecting the absorption, distribution, metabolism, or elimination of the study drugs (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.). Past or Concurrent Medications/Treatments: 9.Prior allogeneic stem cell or solid organ transplantation. 10.Concurrent use of medications known to prolong the QTc interval and/or induce Torsades de Pointes (TdP), or drugs that may affect drug metabolism. 11.Past or current congenital or acquired immunodeficiency diseases. 12.Active or documented history of autoimmune or inflammatory diseases (including but not limited to autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyper- or hypothyroidism, asthma requiring bronchodilators, etc.). Patients with vitiligo or childhood asthma that has completely resolved in adulthood without any intervention may be included. Safety: 13.Known or suspected history of allergy to JAK inhibitors, donafenib, anti-PD-1 antibodies, or drugs of the same class, or hypersensitivity to any excipient of the study drugs. 14.Patients who experienced severe adverse reactions during prior immune checkpoint inhibitor therapy. 15.Active bleeding or coagulation disorders, bleeding tendency, or current use of thrombolytic, anticoagulant, or antiplatelet therapies. 16.Thrombotic or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc. 17.History of bleeding events from esophageal or gastric varices due to portal hypertension within the past 6 months, or any life-threatening bleeding event within the past 3 months. 18.Clinically significant cardiovascular diseases, including but not limited to acute myocardial infarction within the past 6 months, severe/unstable angina or coronary artery bypass grafting, congestive heart failure (New York Heart Association [NYHA] Class > 2), poorly controlled or pacemaker-requiring arrhythmias, or uncontrolled hypertension (systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg). 19.Other clinically significant abnormalities in clinical or laboratory findings deemed by the investigator to impact safety evaluation, such as uncontrolled diabetes, chronic kidney disease, Grade 2 or higher peripheral neuropathy (CTCAE V5.0), abnormal thyroid function, etc. 20. Active or poorly controlled severe infections; active infections including: a.Human Immunodeficiency Virus (HIV) (HIV1/2 antibody) positive; b.Active Hepatitis B (HBsAg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;Progression-free survival;Disease control rate;Adverse events;Serious adverse events; | — |
Countries
China
Contacts
Public ContactZha Yong
Yunnan Cancer Hospital
Outcome results
None listed