Conversion Therapy With FOLFOX-HAIC Plus Lenvatinib And Tislelizumab For Hepatocellular Carcinoma With Vp3 Portal Vein Tumor Thrombus

NCT07483359 | Recruiting Phase 2

• 1 other identifier: 2026-CONV3RSION-01
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma (HCC); Portal Vein Tumor Thrombus

Keywords

Conversion Therapy; Hepatic Arterial Infusion Chemotherapy; Tislelizumab; Lenvatinib; Vp3 Portal Vein Tumor Thrombus

Outcome Measures

Primary Outcomes (1)

• Technical 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).

  Up to approximately 2 years.

Secondary Outcomes (11)

• 1-Year Overall Survival (OS) Rate

  12 months from the first dose of study treatment.

• Progression-Free Survival (PFS) per RECIST v1.1

  Up to approximately 2 years.

• Progression-Free Survival (PFS) per mRECIST

  Up to approximately 2 years.

• Time to Progression (TTP) per RECIST v1.1

  Up to approximately 2 years.

• Time to Progression (TTP) per mRECIST

  Up to approximately 2 years.

Study Arms (1)

HAIC plus lenvatinib and tislelizumab

EXPERIMENTAL

Participants receive a 21-day cycle consisting of intravenous immunotherapy (Tislelizumab), local hepatic arterial infusion chemotherapy (FOLFOX-HAIC), and daily oral targeted therapy (Lenvatinib).

Combination Product: HAIC + Tislelizumab +lenvatinib

Interventions

HAIC + Tislelizumab +lenvatinib COMBINATION_PRODUCT

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.

HAIC plus lenvatinib and tislelizumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from the study:
• History of other active malignancies within 5 years (except for adequately treated basal cell carcinoma of the skin or papillary thyroid cancer).
• Evidence of extrahepatic metastasis confirmed by chest, abdomen, and pelvis CT and/or MRI scans.
• Presence of clinically significant ascites.
• History of hepatic encephalopathy.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan at screening.
• Severe infection within 4 weeks prior to enrollment, including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia.
• History of hypertensive crisis; or major cardiovascular disease within 3 months prior to starting study treatment (e.g., New York Heart Association \[NYHA\] Class II or worse heart failure, myocardial infarction, cerebrovascular accident, unstable arrhythmia, or unstable angina).
• Inadequately controlled arterial hypertension, defined as systolic blood pressure (BP) ≥ 150 mmHg and/or diastolic BP \> 100 mmHg (based on an average of ≥ 3 BP readings obtained from ≥ 2 measurements). Achieving these parameters through the use of antihypertensive therapy is permitted.
• Severe vascular disease within 6 months (e.g., aortic aneurysm requiring surgical repair or peripheral arterial thrombosis); or a current or recent history of active autoimmune disease or immunodeficiency (including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis).
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the investigational drugs, may affect the interpretation of the results, or may place the patient at high risk for treatment-related complications.
• Use of systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or the expected need for long-term systemic immunosuppressive therapy during the study. Exceptions permitting the use of corticosteroids include: (1) prophylactic use to prevent allergic reactions to imaging contrast media (e.g., short-term dexamethasone); (2) topical, ophthalmic, intra-articular, otic, or inhaled corticosteroids with minimal systemic absorption; (3) physiological replacement doses of systemic corticosteroids (defined as ≤ 10 mg/day of prednisone or an equivalent corticosteroid).
• Evidence of bleeding diathesis or severe coagulopathy.
• Patients preparing to undergo, or who have previously received, a solid organ or allogeneic bone marrow transplant.

Sponsors & Collaborators

• Liaoning Cancer Hospital & Institute: collaborator
• The Affiliated Hospital of Yanbian University: collaborator
• First Hospital of China Medical University: lead

Study Sites (1)

The First Hospital of China Medical University

Shenyang, Liaoning, 110000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Kai Li, MD, PhD

  First Hospital of China Medical University

  PRINCIPAL INVESTIGATOR

• Haibo Shao, MD, PhD

  First Hospital of China Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haibo Shao, MD, PhD

CONTACT

+8613840150051; hbshao@cmu.edu.cn

Jiaxi Liu, MD

CONTACT

+8618940279150; dmuvictor@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 16, 2026
• First Posted: March 19, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)