Efficacy and Safety of Multimodal Ablation Combined With PD-1 Monoclonal Antibody, Lenvatinib and TACE in the Treatment of Unresectable Primary Hepatocellular Carcinoma: A Single-Arm, Single-Center Clinical Study

This study is a prospective, single-arm, single-center trial evaluating the efficacy of TACE combined with multimodal ablation, Tislelizumab, and lenvatinib in the treatment of unresectable primary liver cancer.

Study Overview

• Status: Recruiting
• Conditions: Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Carcinoma, Hepatocellular; Liver Neoplasms
• Intervention / Treatment: Device: Multimodal Thermal Therapy

Detailed Description

This study aims to evaluate the efficacy and safety of multimodal ablation combined with Tislelizumab, lenvatinib, and TACE in the treatment of primary liver cancer. By comparing preoperative and postoperative immune markers, the study seeks to clarify the clinical value of multimodal ablation combined with systemic therapy and TACE in the management of primary liver cancer.

• Study Type: Interventional
• Enrollment (Estimated): 17
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhiping Yan, M.D; Phone Number: +86 13122806500; Email: yan.zhiping@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital, Fudan University
      • Contact: Minjie Yang; Phone Number: +86 02164041990; Email: yang.mingjie@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80 years, regardless of gender.
2. Clinically or pathologically confirmed HCC.
3. CNLC stage IIb-IIIa, deemed unresectable after multidisciplinary evaluation.
4. Having radiologically evaluable, untreated target lesions for ablation, with the largest diameter of the target tumor >5 cm.
5. Patients who have not undergone systemic chemotherapy, targeted therapy, or immunotherapy for hepatocellular carcinoma, or those who have been evaluated as SD (stable disease) or PD (progressive disease) after treatment..
6. ECOG PS 0-1 and an expected survival >3 months.
7. Child-Pugh score ≤7.

Exclusion Criteria:

1. Child-Pugh class C liver dysfunction.
2. Tumor thrombus in the main portal vein or hepatic vein.
3. Extensive metastatic disease with an expected survival <3 months.
4. Severe dysfunction of major organs (liver, kidney, heart, lung, or brain).
5. History of esophageal/gastric variceal bleeding within the past month.
6. History of other malignancies.
7. Last anti-tumor therapy (e.g., radiotherapy, systemic chemotherapy, or local treatment) within <1 month.
8. Active infection; HBV co-infection (HBV DNA ≥2000 IU/mL or ≥10⁴ copies/mL unless reduced by one log after antiviral therapy); HCV co-infection requiring guideline-directed antiviral treatment; HIV infection; or biliary tract inflammation.
9. History of organ transplantation or hepatic encephalopathy.
10. Uncorrectable coagulation disorders.
11. Refractory massive ascites, pleural effusion, or cachexia.
12. Pregnancy, impaired consciousness, or inability to comply with treatment.
13. High tumor burden (sum of the largest liver lesion diameter and number of liver lesions >12).
14. Any other condition deemed unsuitable by investigators that may affect study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Group; The patient will receive induction therapy with tislelizumab and lenvatinib within 14 days after enrollment. Subsequently, within 2-7 days (the exact timing will be determined based on clinical circumstances), they will undergo Multimodal Thermal Therapy (MTT). Following the MTT procedure, on-demand TACE treatment will be administered. Starting from day 7 post-MTT (with the exact timing adjusted according to clinical conditions), the patient will resume tislelizumab and lenvatinib therapy until disease progression, occurrence of intolerable toxicity, or withdrawal of consent.

Device: Multimodal Thermal Therapy; The high-burden tumor is identified as the target lesion for treatment. A pre-treatment biopsy of the target lesion is performed to obtain tumor tissue. Multimodal ablation therapy of the target lesion is conducted under CT guidance. The treatment procedure follows the tumor ablation protocol using the multimodal therapy radiofrequency temperature-controlled mode.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) according to RECIST 1.1 and mRECIST	Refers to the proportion of patients whose tumors shrink to a certain extent and maintain that response for a specified period, including cases of Complete Response (CR) and Partial Response (PR). Tumor objective response is assessed using RECIST 1.1 and mRECIST criteria. At baseline, subjects must have measurable tumor lesions. According to the efficacy evaluation criteria, the outcomes are classified as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD).	Follow-up for 12 months, with evaluations conducted at 2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 12 months postoperatively.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival（PFS）	It refers to the time from the date of enrollment to the date of the first recorded disease progression(PD)or death,whichever occurs first.	Follow-up for 12 months,with assessments conducted every 3 months.
Overall Survival（OS）	Overall Survival(OS)refers to the time from the date of enrollment to the date of death due to any cause.	Follow-up for 12 months,with assessments conducted every 3 months.
Safety and Tolerability	Safety:Refers to the extent to which a drug does not cause unacceptable harm or side effects when applied in the human body.Tolerability:Refers to the degree to which patients accept the side effects that occur after treatment,reflecting their ability to endure the side effects of the medication.All adverse events will be recorded and assessed for severity based on the NCI-CTC AE 5.0 grading criteria.During the follow-up period,all subjects will be continuously monitored,and the occurrence,duration,severity,and treatment-relatedness of adverse events will be documented.	Follow-up for 12 months, with evaluations conducted at 2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 12 months postoperatively.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: TACE; lenvatinib; Tislelizumab; Multimodal; unresectable primary liver cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Diseases; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms
• Other Study ID Numbers: MTT-B2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No