HAIC Combined with Donafenib and Sintilimab As Perioperative Treatment for Resectable Hepatocellular Carcinoma Patients At High Risk of Recurrence

Exclusion Criteria

• •Patients with distant metastasis.
• •Patients with portal vein tumor thrombosis (Vp3-Vp4).
• •History of any other malignant tumor within the past 5 years, unless the patient has received potentially curative treatment and there is no evidence of recurrence in the past 5 years. This 5-year time requirement does not apply to patients who have successfully undergone resection for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ.
• •History or current presence of congenital or acquired immunodeficiency diseases.
• •Active or previously documented autoimmune diseases or inflammatory disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, pituitary inflammation, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators for treatment, etc.). Patients with vitiligo or asthma fully resolved in childhood and not requiring intervention as adults may be included.
• •History of severe psychiatric disorders.
• •Conditions affecting the absorption, distribution, metabolism, or elimination of the study drugs (e.g., severe vomiting, chronic diarrhea, bowel obstruction, malabsorption, etc.).
• •Major surgery within 4 weeks prior to enrollment (as defined by the investigator).
• •History of allogeneic stem cell or solid organ transplantation (except for corneal transplantation).
• •Received other systemic antitumor therapies (including traditional Chinese medicine with antitumor indications) within 2 weeks or 5 half-lives (whichever is longer) prior to study drug administration, or unresolved adverse events related to prior treatments that have not recovered to ≤ CTCAE Grade 1.
• •Use of systemic immunosuppressive drugs within 2 weeks prior to enrollment, or anticipated need for systemic immunosuppressive therapy during the study.
• •Concurrent use of drugs that may prolong the QTc interval and/or induce Tdp, or drugs affecting drug metabolism.
• •Known or suspected allergy to donafenib, recombinant humanized PD-1 monoclonal antibodies, or similar agents, or a history of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to excipients of the study drugs.
• •Uncontrolled hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion, or pericardial effusion.
• •Active bleeding or coagulation disorders, bleeding tendencies, or ongoing treatment with thrombolytics, anticoagulants, or antiplatelet therapy.
• •History of gastrointestinal bleeding or clear gastrointestinal bleeding tendencies within the past 6 months (e.g., known active ulcerative lesions, positive stool occult blood with ≥2+ results, requiring endoscopy if stool occult blood remains positive), or other conditions that may lead to gastrointestinal bleeding as determined by the investigator (e.g., severe esophageal/gastric varices).
• •History of gastrointestinal perforation, abdominal fistulas, or intra-abdominal abscesses within the past 6 months.
• •History of thrombosis or thromboembolic events (e.g., stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the past 6 months.
• •Significant cardiovascular disease, including but not limited to: acute myocardial infarction, severe/uncontrolled angina, coronary artery bypass grafting within the past 6 months; congestive heart failure (NYHA class \>2); poorly controlled arrhythmias requiring pacemaker treatment; drug-resistant hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg).
• •Active infection.
• •Other significant clinical or laboratory abnormalities that may affect safety evaluation, such as uncontrolled diabetes, chronic kidney disease, grade 2 or higher peripheral neuropathy (CTCAE v5.0), thyroid dysfunction, etc.
• •Use of live attenuated vaccines within 4 weeks prior to enrollment or during the study.
• •Pregnant or breastfeeding women, or women or men of childbearing potential unwilling or unable to use effective contraception.
• •History of alcohol, drug, or substance abuse within the past 6 months.
• •Participation in any other clinical trial involving investigational drugs or medical devices within 4 weeks prior to enrollment.
• •Inability to comply with the study protocol for treatment or follow-up visits.
• •Any other conditions that, in the opinion of the investigator, would preclude participation in the study.