Conversion Therapy With FOLFOX-HAIC Plus Lenvatinib and Tislelizumab for Hepatocellular Carcinoma With Vp3 Portal Vein Tumor Thrombus: A Prospective, Multicenter, Single-arm Study
Patients with hepatocellular carcinoma (HCC) complicated by Vp3 portal vein tumor thrombus (PVTT) face a poor prognosis and are typically ineligible for surgical resection. This prospective study evaluates a conversion therapy regimen-utilizing a combination of FOLFOX-HAIC, Lenvatinib, and Tislelizumab-designed to induce significant regression of both the tumor burden and the PVTT. The primary objective is to determine the Technical Resectability Rate (TRR), assessing the potential for this triple-combination therapy to downstage initially unresectable disease to a state suitable for curative-intent R0 surgical resection.
• Participants must meet all of the following inclusion criteria to be enrolled in this trial:
• Voluntarily sign the written informed consent form.
• Age 18 to 80 years (inclusive), male or female.
• Histologically or cytologically confirmed Hepatocellular Carcinoma (HCC) according to the Clinical Practice Guideline for Primary Liver Cancer (2024 Edition), and evaluated by a Multi-Disciplinary Team (MDT) as initially unresectable.
• No prior systemic anti-tumor therapy (including targeted therapy, immunotherapy, and systemic chemotherapy).
• Barcelona Clinic Liver Cancer (BCLC) stage C and China Liver Cancer (CNLC) stage IIIa, complicated with imaging-confirmed Vp3 portal vein tumor thrombus (PVTT, defined as tumor thrombus invading the first-order branches of the portal vein but not the main trunk).
• At least one measurable target lesion according to RECIST v1.1 criteria.
• Expected survival time of ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
• Child-Pugh liver function class A or B (score ≤ 7).
⁃ Adequate major organ function, meeting the following baseline laboratory criteria:
∙ Hematology: Hemoglobin ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 x 10\^9/L; Platelet count ≥ 75 x 10\^9/L.
‣ Biochemistry: Albumin ≥ 28 g/L; Total Bilirubin ≤ 3 x Upper Limit of Normal (ULN); AST and ALT ≤ 5 x ULN; Alkaline Phosphatase (ALP) ≤ 5 x ULN; Serum Creatinine ≤ 1.5 x ULN.
‣ Coagulation: INR or Prothrombin Time (PT) ≤ 1.5 x ULN; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 x ULN.
⁃ Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment, must not be breastfeeding, and must agree to use highly effective contraception during the study treatment and for at least 6 months after the last dose.
⁃ Good compliance and willingness to cooperate with all study-related follow-up procedures.
⁃ Assessed by the MDT as Potentially Resectable according to the Chinese expert consensus on conversion and perioperative therapy of primary liver cancer (2024 edition). This is defined as participants who are temporarily unsuitable for upfront surgical resection due to oncological factors (e.g., Vp3 PVTT indicating a high risk of early post-operative recurrence) or technical factors (e.g., massive tumor size leading to insufficient future liver remnant \[FLR\]), but who are expected to convert to an R0 resection and achieve significant clinical benefit following downstaging with the combination of FOLFOX-HAIC and systemic therapy.