TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol for Unresectable HCC With Cirrhotic Portal Hypertension

NCT07350070 | Not Yet Recruiting Phase 2

• 1 other identifier: CHALLENGE-05
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 7

Brief Summary

In China, the majority of hepatocellular carcinoma (HCC) cases stem from chronic hepatitis B virus (HBV) infection and subsequent cirrhosis, with patients often presenting at the decompensated stage complicated by clinically significant portal hypertension (CSPH). CSPH not only limits treatment options and worsens prognosis but also leads to the frequent exclusion of such patients from pivotal clinical trials, resulting in a lack of high-level evidence for their management. Carvedilol, a non-selective beta-blocker, is a first-line therapy for portal hypertension. Emerging evidence suggests that this drug class may also modulate the tumor microenvironment and enhance the efficacy of immune checkpoint inhibitors. To address this unmet need, this study aims to explore a novel quadruple-therapy strategy (TACE + tislelizumab + lenvatinib + carvedilol) for the treatment of unresectable HCC with concurrent cirrhotic portal hypertension. The rationale is twofold: while controlling portal hypertension and safeguarding treatment safety, carvedilol may also potentiate immunotherapy by modulating adrenergic signaling, thereby achieving dual benefits of "liver protection" and "anti-cancer" synergy. Utilizing an efficient Simon's two-stage design, this study will conduct a preliminary assessment of the regimen's efficacy and safety with minimal risk, providing essential data to inform future confirmatory research.

Conditions

HCC; Liver Cirrhosis; Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  ORR is defined as the proportion of patients who achieved the best therapeutic response of PR or CR among all the patients enrolled.

  From the date of enrollment, until the tumor progresses, the patient dies, or the study concludes (whichever occurs first), the assessment period can last up to 60 months.

Secondary Outcomes (4)

• Progression-free survival(PFS)

  From the date of enrollment, until the tumor progresses, the patient dies, or the study concludes (whichever occurs first), the assessment period can last up to 60 months.

• Overall survival(OS)

  From the date of enrollment, until the patient dies, the assessment period can last up to 60 months.

• Adverse events (AEs)

  From the baseline up to 12 months.

• The rate of decompensation of liver cirrhosis

  From the date of enrollment, until the patient dies, or the study concludes (whichever occurs first), the assessment period can last up to 60 months.

Other Outcomes (1)

• Difference in treatment effect (Hazard Ratio) between participants with emotional disorders versus non-emotional disorders, assessed by the interaction p-value.

  From baseline until death, study conclusion, or up to 60 months (whichever occurs first).

Study Arms (1)

TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol arm

EXPERIMENTAL

1. TACE On-demand TACE: Use 1-2 sessions of TACE depending on the tumor condition. 2. PD-1 inhibitor Tislelizumab 200 mg intravenous infusion, once every 3 weeks 3. Lenvatinib Formulation: Tablets; Specifications: 4mg/tablet 8mg (for patients weighing less than 60kg) or 12mg (for patients weighing more than 60kg) once daily, taken half an hour after meals (the time of taking the medication should be as consistent as possible), discontinue medication during TACE treatment 4. Carvedilol Formulation: Tablets; Specifications: 6.25mg/tablet Initial dose is 6.25mg, and the maintenance dose is 6.25mg - 12.5mg/day. For patients with combined arterial hypertension or heart disease, the dose of carvedilol can be further increased to treat non-liver indications.

Drug: TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol

Interventions

TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol DRUG

All the enrolled patients received standard first-line treatment (TACE combined with tiragolumab and lenvatinib) and were additionally treated with carvedilol. The treatment duration of the study was one year. After the end of the treatment, the patients would be evaluated by the researchers to determine whether to continue the treatment or switch to other first-line treatments.

TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-75 years.
• At least one radiologically measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (tumor lesion long axis ≥10 mm on CT scan).
• Newly diagnosed hepatocellular carcinoma without any prior treatment for HCC.
• Child-Pugh liver function score ≤ 7.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
• Absence of severe organic diseases affecting major organs (e.g., heart, lung, brain).
• Compensated cirrhosis with clinically significant portal hypertension (meeting any one of the following criteria):
• Imaging evidence (ultrasound, CT, or MRI) of portosystemic collateral circulation.
• Endoscopic evidence of esophageal or gastric varices.
• Liver stiffness measurement (LSM) \>25 kPa; or LSM 20-25 kPa with platelet count \<150×10⁹/L; or LSM 15-20 kPa with platelet count \<110×10⁹/L.

You may not qualify if:

• Decompensated cirrhosis.
• Concurrent other malignancies or recurrent HCC.
• Any active, known, or suspected autoimmune disease.
• History of allergy to any component of PD-1 inhibitors, lenvatinib, or carvedilol.
• Severe concurrent medical conditions, including asthma, significant cardiac conduction block, and sinus bradycardia.
• Known human immunodeficiency virus (HIV) infection; or active hepatitis (e.g., hepatitis B/C virus infection).
• Presence of tumor thrombus in the inferior vena cava, hepatic vein, or main portal vein.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (7)

Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Department of Hepatobiliary and Pancreatic Oncology

Fuzhou, Fujian, China

Location

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Hubei Province Tahe Hospital

Taihe, Hubei, China

Location

Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

Location

Organ Transplant Department,Qilu Hospital, Cheeloo College of Medicine, Shandong University,

Jinan, Shandong, 250012, China

Location

Shandong First Medical University Affiliated Provincial Hospital

Jinan, Shandong, China

Location

Qingdao University Affiliated Hospital

Qingdao, Shandong, China

Location

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Interventions

tislelizumab; lenvatinib; Carvedilol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Wanguang Zhang

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wanguang Zhang

CONTACT

13886195965; wgzhang@tjh.tjmu.edu.cn

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

Model Details: This study is a multicenter, single-arm, Simon two-stage design phase II clinical trial, aiming to evaluate the efficacy and safety of the combined TACE with tislelizumab, lenvatinib and carvedilol in the treatment of unresectable hepatocellular carcinoma (uHCC) patients with liver cirrhosis and portal hypertension. The study plans to recruit a total of 78 patients. The optimal two-stage design is adopted: 23 patients will be enrolled in the first stage. If the objective response rate (ORR, based on mRECIST v1.1) does not reach the preset threshold (≤ 11 responses) then the trial will be prematurely terminated; if it reaches (≥ 12 responses), then the second stage will continue with the enrollment of 55 more patients. Finally, if the number of patients achieving response in the total population is ≥ 43, then the scheme is considered effective.

Study Record Dates

• First Submitted: December 25, 2025
• First Posted: January 20, 2026
• Study Start: December 31, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

CN (7)