Tauroursodeoxycholic Acid Combined With PD-1/PD-L1 Immunotherapy in Advanced Hepatocellular Carcinoma: A Prospective Study

NCT07064668 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TJ-IRB202505056
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clinical trial that aims to evaluate whether adding a bile acid called tauroursodeoxycholic acid (TUDCA) can improve the effects of immunotherapy in patients with advanced liver cancer (hepatocellular carcinoma). Immunotherapy has shown promise in treating this type of cancer, but not all patients respond well. TUDCA is known to help protect liver cells and may improve the liver's immune environment, potentially making immunotherapy more effective. In this study, 300 patients with advanced liver cancer will be randomly assigned to receive either immunotherapy alone or immunotherapy combined with TUDCA. Researchers will look at how well the cancer responds, whether the treatment helps more patients become eligible for surgery, and how safe the combination is. The goal is to find a more effective and better tolerated treatment for patients with liver cancer.

Conditions

Hepatocellular Carcinoma

Keywords

tumor immunotherapy; Bile acid metabolism; tauroursodeoxycholic acid

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  Time from randomization to death from any cause.

  Up to 12 months

• Progression-Free Survival (PFS)

  Time from randomization to disease progression or death from any cause, assessed by RECIST 1.1 criteria.

  Up to 12 months

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  up to 12 months

• Change in Renal Function Indicators

  From baseline to 12 weeks (every 4-6 weeks)

• Change in Hematologic Parameters

  From baseline to 12 weeks (every 4-6 weeks)

• Change in Immune Inflammatory Markers

  From baseline to 12 weeks (every 4-6 weeks)

• Change in Serum Bile Acid Levels

  From baseline to 12 weeks (every 4-6 weeks)

Study Arms (2)

TUDCA + ICI

EXPERIMENTAL

Participants will receive a combination of tauroursodeoxycholic acid (TUDCA) and an immune checkpoint inhibitor.

Drug: TUDCA (Tauroursodeoxycholic Acid) Supplementation; Drug: Immune checkpoint inhibitor (ICI)

ICI Monotherapy

ACTIVE COMPARATOR

Participants will receive standard immune checkpoint inhibitor monotherapy.

Drug: Immune checkpoint inhibitor (ICI)

Interventions

TUDCA (Tauroursodeoxycholic Acid) Supplementation DRUG

TUDCA administered orally according to protocol-defined dosage.

TUDCA + ICI

Immune checkpoint inhibitor (ICI) DRUG

Administered intravenously according to standard practice or protocol.

ICI Monotherapy; TUDCA + ICI

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of primary hepatocellular carcinoma (HCC).
• Unresectable advanced HCC classified as Barcelona Clinic Liver Cancer (BCLC) stage C.
• Age ≥ 18 years.
• No prior systemic anti-tumor therapy for HCC before first dose of study treatment.
• At least one measurable lesion according to RECIST v1.1, or a measurable lesion with clear progression after local treatment based on RECIST v1.1.
• Adequate organ and bone marrow function within 7 days prior to enrollment, with no blood products, growth factors, albumin, or other intravenous/subcutaneous corrective treatment within 14 days prior to laboratory assessment:
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count (PLT) ≥ 75 × 10⁹/L Hemoglobin (Hb) ≥ 9.0 g/dL
• Liver function:
• Total bilirubin (TBil) ≤ 2 × ULN ALT and AST ≤ 5 × ULN Serum albumin ≥ 28 g/L
• Alkaline phosphatase (ALP) ≤ 5 × ULN
• Renal function:
• Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min (calculated by Cockcroft-Gault formula) Urinalysis shows urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine collection must show protein \< 1g/24h
• Coagulation:
• International Normalized Ratio (INR) ≤ 2.3 or prothrombin time (PT) prolongation ≤ 6 seconds

You may not qualify if:

• History of hepatic encephalopathy or liver transplantation.
• Acute cholecystitis, acute cholangitis, patients with frequent biliary colic attacks, complete biliary obstruction, or gallbladder dysfunction (inability to contract and empty).
• Patients with Child-Pugh class C or decompensated cirrhosis, including those with a history of severe hepatic encephalopathy or refractory ascites due to liver disease.
• Patients with a previous diagnosis of biliary atresia without adequate biliary drainage (e.g., failed biliary-enteric anastomosis).
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Medical college of HUST

Wuhan, Hubei, 430000, China

Location

Related Publications (8)

• Lan X, Ma J, Huang Z, Xu Y, Hu Y. Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism. J Gene Med. 2024 Jan;26(1):e3639. doi: 10.1002/jgm.3639. Epub 2023 Dec 7.

  PMID: 38058259 BACKGROUND

• Kusaczuk M. Tauroursodeoxycholate-Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives. Cells. 2019 Nov 20;8(12):1471. doi: 10.3390/cells8121471.

  PMID: 31757001 BACKGROUND

• Latif MU, Schmidt GE, Mercan S, Rahman R, Gibhardt CS, Stejerean-Todoran I, Reutlinger K, Hessmann E, Singh SK, Moeed A, Rehman A, Butt UJ, Bohnenberger H, Stroebel P, Bremer SC, Neesse A, Bogeski I, Ellenrieder V. NFATc1 signaling drives chronic ER stress responses to promote NAFLD progression. Gut. 2022 Dec;71(12):2561-2573. doi: 10.1136/gutjnl-2021-325013. Epub 2022 Apr 1.

  PMID: 35365570 BACKGROUND

• Oura K, Morishita A, Tani J, Masaki T. Tumor Immune Microenvironment and Immunosuppressive Therapy in Hepatocellular Carcinoma: A Review. Int J Mol Sci. 2021 May 28;22(11):5801. doi: 10.3390/ijms22115801.

  PMID: 34071550 BACKGROUND

• Zheng J, Wang S, Xia L, Sun Z, Chan KM, Bernards R, Qin W, Chen J, Xia Q, Jin H. Hepatocellular carcinoma: signaling pathways and therapeutic advances. Signal Transduct Target Ther. 2025 Feb 7;10(1):35. doi: 10.1038/s41392-024-02075-w.

  PMID: 39915447 BACKGROUND

• Cunningham M, Gupta R, Butler M. Checkpoint inhibitor hepatotoxicity: pathogenesis and management. Hepatology. 2024 Jan 1;79(1):198-212. doi: 10.1097/HEP.0000000000000045. Epub 2023 Jan 13.

  PMID: 36633259 BACKGROUND

• Fleishman JS, Kumar S. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets. Signal Transduct Target Ther. 2024 Apr 26;9(1):97. doi: 10.1038/s41392-024-01811-6.

  PMID: 38664391 BACKGROUND

• Feng L, Zhang W, Shen Q, Miao C, Chen L, Li Y, Gu X, Fan M, Ma Y, Wang H, Liu X, Zhang X. Bile acid metabolism dysregulation associates with cancer cachexia: roles of liver and gut microbiome. J Cachexia Sarcopenia Muscle. 2021 Dec;12(6):1553-1569. doi: 10.1002/jcsm.12798. Epub 2021 Sep 28.

  PMID: 34585527 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

ursodoxicoltaurine; Dietary Supplements; Immune Checkpoint Inhibitors

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

Intervention Hierarchy (Ancestors)

Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Zhanguo Zhang, doctor

CONTACT

+8613517726223; zhanguo_tjh@hust.edu.cn

Shangwu Ning, master

CONTACT

+8613517726223; 13517726223@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: This is a randomized, parallel assignment, controlled interventional study. Eligible participants with advanced hepatocellular carcinoma (BCLC stage C) will be randomly assigned in a 1:1 ratio to receive either standard immune checkpoint inhibitor (ICI) monotherapy or ICI therapy in combination with tauroursodeoxycholic acid (TUDCA). The study will assess efficacy and safety over a 6-month treatment period with follow-up extending to 12 months post-treatment. No crossover between arms is planned.

Study Record Dates

• First Submitted: July 5, 2025
• First Posted: July 15, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)