IRE After Targeted Immunotherapy in HCC With Portal Vein Tumor Thrombus

A Prospective, Randomized Controlled Phase II Clinical Study of Sequential or Non-sequential Irreversible Electroporation After Targeted Immunotherapy Induction in Patients With Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

This is a prospective, randomized, controlled, exploratory Phase II clinical study. Approximately 60 eligible patients with hepatocellular carcinoma and portal vein tumor thrombus who have received three cycles of target-immunotherapy induction and have non-progressive disease will be enrolled. All patients must be considered unresectable or unable to tolerate surgical resection by MDT review and must provide written informed consent. Participants will be randomized 2:1. Forty patients will undergo open or percutaneous IRE followed by continuation of the original target-immunotherapy regimen; twenty patients will continue the original treatment regimen alone. OS, PFS, tumor response, QoL, safety, and postoperative outcomes will be observed.

Inclusion Criteria:

• Age 18-75 years, any sex
• Imaging-confirmed or histologically confirmed primary liver cancer/hepatocellular carcinoma (HCC)
• After three cycles of target-immunotherapy induction, MDT review determines unresectable disease or inability to tolerate surgical resection
• Willingness to receive standard conversion treatment
• No prior palliative targeted immunotherapy or other systemic antitumor therapy
• Maximum tumor diameter <=5 cm and number of tumors <=5
• No extrahepatic metastasis; portal vein tumor thrombus Vp1-3
• At least one measurable lesion according to RECIST 1.1
• Adequate organ and marrow function: hemoglobin >=9.0 g/dL; neutrophils >=1.5 x 10^9/L; platelets >=100 x 10^9/L; TBIL <=3 x ULN; AST and ALT <=5.0 x ULN; serum creatinine <=1.5 x ULN or CrCl >60 mL/min by Cockcroft-Gault formula
• ECOG Performance Status 0-1
• Expected survival of at least 3 months
• Patients of childbearing potential and their partners agree to use contraception
• Voluntary written informed consent

Exclusion Criteria:

• Refusal to receive systemic therapy or possible surgery
• Metastasis to other sites, such as lymph nodes, peritoneum, lung, bone, or brain
• History of other malignancies, except cured basal cell carcinoma of the skin or cervical carcinoma in situ
• Severe uncontrolled comorbidities, including uncontrolled congestive heart failure (NYHA III/IV), unstable angina, poorly controlled arrhythmia, uncontrolled hypertension, active infection, uncontrolled diabetes, uncontrolled pleural effusion/pericardial effusion/ascites requiring drainage, severe portal hypertension or portal cavernoma on imaging, gastric outlet obstruction, or respiratory insufficiency requiring oxygen
• Major surgery within 30 days before screening
• EGFR monoclonal antibody or EGFR-TKI within 30 days before screening
• Allergy to any drug or component used in this protocol
• Known or self-reported HIV infection or chronic hepatitis B or hepatitis C
• Unresolved toxicity >=CTCAE grade 2 from prior treatment, except anemia, alopecia, skin pigmentation, or chemotherapy-induced neurotoxicity
• Any other reason judged by the investigator to make participation inappropriate