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.
This prospective, multicenter, single-arm clinical trial evaluates the efficacy and safety of a triple-combination conversion therapy for patients with initially unresectable hepatocellular carcinoma (HCC) complicated by Vp3 portal vein tumor thrombus (PVTT). The study aims to enroll 38 participants to assess the technical resectability rate (TRR) as the primary endpoint. Participants undergo a 21-day treatment cycle consisting regimens of intravenous Tislelizumab, FOLFOX-based hepatic arterial infusion chemotherapy (HAIC), while receiving daily oral Lenvatinib. This combination is designed to leverage the synergistic effects of high-concentration local chemotherapy and systemic targeted-immunotherapy to induce significant regression of both the tumor burden and the PVTT. The clinical pathway centers on regular response evaluations conducted every two cycles using multimodal radiological imaging. During these intervals, a dual-evaluation mechanism is employed: a Multi-Disciplinary Team (MDT) reviews the clinical and radiological data to guide real-time surgical decision-making, while a Blinded Independent Review Committee (IRC) independently evaluates the scans to formally determine the primary endpoint of technical resectability. This assessment focuses on anatomical feasibility for R0 resection, the adequacy of the future liver remnant, and the successful downstaging of the PVTT. Patients meeting the clinical conversion criteria proceed to curative-intent surgical intervention, followed by a pathological complete response (pCR) assessment. For participants who remain technically unresectable but continue to demonstrate clinical benefit, the HAIC intervention is limited to a maximum of six cycles. In these cases, systemic targeted and immunotherapy are maintained until disease progression, intolerable toxicity, or a maximum treatment duration of 24 months. The study officially concludes upon the earliest occurrence of either: the completion of the protocol-defined one-year overall survival follow-up for the final enrolled participant (including the achievement of the pre-specified data cutoff), or the point at which all surviving participants have experienced definitive disease progression or death and further data collection is no longer required.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Tislelizumab: 200 mg administered intravenously each 21-day cycle. FOLFOX-HAIC: Administered every 21 days for up to a maximum of 6 cycles. The regimen consists of Oxaliplatin 85 mg/m², Leucovorin 400 mg/m², and 5-Fluorouracil 2500 mg/m² given as a continuous hepatic arterial infusion over 46-48 hours. Lenvatinib: Administered orally once daily on a continuous basis. Dosing is weight-adjusted: 12 mg/day for patients weighing ≥60 kg, and 8 mg/day for patients weighing \<60 kg.
The First Hospital of China Medical University
Shenyang, Liaoning, China
RECRUITINGTechnical Resectability Rate (TRR)
The percentage of participants whose disease converts from initially unresectable to technically resectable, as evaluated by a Blinded Independent Review Committee (IRC) based on multimodal radiological imaging. The criteria for successful conversion include the anatomical feasibility of achieving an R0 resection, the adequacy of the future liver remnant (FLR), and the successful downstaging of the Vp3 portal vein tumor thrombus (PVTT).
Time frame: Up to approximately 2 years.
1-Year Overall Survival (OS) Rate
The percentage of participants who remain alive at 12 months from the date of the first dose of study treatment.
Time frame: 12 months from the first dose of study treatment.
Progression-Free Survival (PFS) per RECIST v1.1
Time from the first dose of study treatment to the first documented objective disease progression, as assessed by the IRC using RECIST v1.1 criteria, or death from any cause, whichever occurs first.
Time frame: Up to approximately 2 years.
Progression-Free Survival (PFS) per mRECIST
Time from the first dose of study treatment to the first documented objective disease progression, as assessed by the IRC using modified RECIST (mRECIST) criteria for hepatocellular carcinoma, or death from any cause, whichever occurs first.
Time frame: Up to approximately 2 years.
Time to Progression (TTP) per RECIST v1.1
Time from the first dose of study treatment to the first documented objective disease progression, as assessed by the IRC using RECIST v1.1 criteria.
Time frame: Up to approximately 2 years.
Time to Progression (TTP) per mRECIST
Time from the first dose of study treatment to the first documented objective disease progression, as assessed by the IRC using modified RECIST (mRECIST) criteria for hepatocellular carcinoma.
Time frame: Up to approximately 2 years.
Objective Response Rate (ORR) per RECIST v1.1
The percentage of participants who achieve a confirmed Complete Response (CR) or Partial Response (PR), as assessed by the Blinded Independent Review Committee (IRC) using RECIST v1.1 criteria. To be considered a confirmed response, the CR or PR must be maintained and verified by a subsequent radiological assessment conducted at least 4 weeks (28 days) after the initial response criteria are met.
Time frame: Up to approximately 2 years.
Objective Response Rate (ORR) per mRECIST
The percentage of participants who achieve a confirmed Complete Response (CR) or Partial Response (PR), as assessed by the Blinded Independent Review Committee (IRC) using modified RECIST (mRECIST) criteria, which specifically evaluates viable (arterially enhancing) tumor tissue. To be considered a confirmed response, the CR or PR must be maintained and verified by a subsequent radiological assessment conducted at least 4 weeks (28 days) after the initial response criteria are met.
Time frame: Up to approximately 2 years.
Portal Vein Tumor Thrombus (PVTT) Response Rate
The percentage of participants in the Intent-to-Treat (ITT) population who achieve an objective response in the portal vein tumor thrombus. This is defined as either a PVTT Complete Response (PVTT-CR; complete disappearance of the thrombus with vascular recanalization) or a PVTT Partial Response (PVTT-PR; a downgrade in the Vp classification, such as from Vp3 to Vp2 or Vp1), as evaluated by the IRC using multimodal radiological imaging.
Time frame: Up to approximately 2 years.
Actual Resection Rate (ARR)
The percentage of participants in the Intent-to-Treat (ITT) population who actually undergo and successfully complete a curative-intent R0 surgical resection following the study treatment.
Time frame: Up to approximately 2 years.
Pathological Complete Response (pCR) Rate
The percentage of participants undergoing surgical resection who achieve a pathological complete response (pCR). This is defined as the complete absence of any residual viable tumor cells in both the primary hepatic lesion and the resected portal vein tumor thrombus (PVTT), as confirmed by post-operative histopathological examination of the resected specimens.
Time frame: Up to approximately 2 years.
Incidence and Severity of Adverse Events (AEs)
The number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) will be recorded. The severity of all AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Special attention will be given to tracking adverse events of special interest (AESIs), including HAIC-related complications and immune-related adverse events (irAEs).
Time frame: Through 30 days after the last dose of study treatment (up to 2 years).
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