Epalrestat Combined With HAIC, Donafenib and Tislelizumab as First-line Treatment for Patients With Unresectable HCC and Diabetes

A Multicenter, Prospective, Single-arm Clinical Study Evaluating the Efficacy and Safety of Epalrestat Combined With Hepatic Arterial Chemotherapy Infusion (HAIC), Donafenib and Tislelizumab as First-line Treatment for Patients With Unresectable Hepatocellular Carcinoma and Diabetes

The purpose of this study is to evaluate the comprehensive therapeutic efficacy and safety profile of the epalrestat combined with hepatic artery infusion chemotherapy (HAIC), donafenib and tislelizumab quadruple regimen in patients with unresectable hepatocellular carcinoma (HCC) and diabetes.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes; HCC - Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Epalrestat; Drug: Donafenib + Tislelizumab; Procedure: HAIC

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongbin Zou; Phone Number: +8618040026871; Email: hongbinzou300@gmail.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • The First Hospital of China Medical University
      • Contact: Haibo Shao; Phone Number: +8613840150051; Email: haiboshao@aliyun.com
      • Contact: Tao Han; Phone Number: 8617790995045; Email: than1984@sina.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diabetes mellitus combined with unresectable advanced HCC (BCLC stage C);
2. Patients who have the need for treatment, prevention and improvement of diabetic neuropathy;
3. Liver function at Child-Pugh grade A or B (≤ 7 points), ECOG PS 0-1;
4. Age 18-80 years old. Confirmed as unrectable HCC through pathological or imaging diagnosis;

Exclusion Criteria:

1. Severe liver dysfunction: Child-Pugh C grade (≥ 8 points) or active hepatic encephalopathy Illness;
2. Extensive extrahepatic metastases (e.g., lung, bone, or peritoneum metastases);
3. Severe cardiovascular diseases: Uncontrolled heart failure, recent myocardial infarction;
4. Renal failure: Creatinine clearance rate < 30 mL/min;
5. Thrombocytopenia (less than 50×10⁹/L) or coagulation dysfunction (INR greater than 1.5);
6. Active infection (such as uncontrolled hepatitis B virus replication with HBV-DNA > 2000 IU/mL);
7. ECOG PS ≥ 2 or extremely poor overall condition;
8. Diabetic patients with acute ketoacidosis or during the period of severe infection;
9. Pregnant and lactating women;
10. Known history of other malignancy.

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: Epalrestat plus HAIC, donafenib and tislelizumab; Epalrestat 50mg tid, donafenib 0.2g bid, tislelizumab 200mg per 21days, HAIC (FOLFOX or RALOX) per 21days

Drug: Epalrestat; For the first 6 patients in the safety lead-in period, the starting dose of epalrestat was 50 mg, three times per day. If dose-limiting toxicity (DLT) occurred in the first 6 patients, the dose for the second round of 6 patients in the safety lead-in period would be adjusted to 50 mg, twice per day. If DLT occurred in the second round of 6 patients, the dose for the third round of 6 patients in the safety lead-in period would be adjusted to 50 mg, once per day.; Drug: Donafenib + Tislelizumab; donafenib 0.2g BID, tislelizumab 200mg/21days; Procedure: HAIC; Include FOLFOX and RALOX.; Other Names: hepatic artery infusion chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month Event-free survival (EFS) Rate	The proportion of patients who have remained event-free from the start of treatment until the 12-month time point.(Predefined events include: progression of disease, death for any reason, terminate the treatment due to intolerable AEs.)	From treatment to the first occurrence of a predefined event (progression of disease, death for any reason, terminate the treatment due to intolerable AEs), assessed up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR) per RESCIST 1.1	The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1.	Up to approximately 2 years
Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0	The percentage and degree of patients who experience at least one AE, whether or not considered related to the treatment, according to CTCAE version 5.0.	Up to approximately 2 years
ORR per mRECIST	The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.	Up to approximately 2 years
Event-free survival (EFS)	Defined as the time from treatment to the first occurrence of a predefined event (progression of disease, death for any reason, terminate the treatment due to intolerable AEs).	From treatment to the first occurrence of a predefined event (progression of disease, death for any reason, terminate the treatment due to intolerable AEs), assessed up to 2 years.
Overall survival (OS)	The OS is defined as the time from the enrollment to death due to any cause.	Up to approximately 2 years
Progression free survival(PFS) (Overall)	The PFS is defined as the time from the enrollment to the first documented progressive disease (according to mRECIST) or death due to any cause, whichever occurs first.	From enrollment to progressive disease (according to mRECIST) or death due to any cause, up to 2 years.
Progression free survival(PFS) of intra-hepatic lesions	The PFS is defined as the time from the enrollment to the first documented progressive disease of intra-hepatic lesions or death due to any cause, whichever occurs first.	From the enrollment to the first documented progressive disease of intra-hepatic lesions or death due to any cause, up to 2 years.
Progression free survival(PFS) of extra-hepatic lesions	The PFS is defined as the time from the enrollment to the first documented appearance of extra-hepatic lesions or death due to any cause, whichever occurs first.	From the enrollment to the first documented appearance of extra-hepatic lesions or death due to any cause, up to 2 years.
PVTT response rate per mRECIST	The PVTT response rate is defined as the proportion of patients with a documented CR or PR of PVTT. According to the Vp classification: CR: PVTT disappears or the portal vein becomes completely unobstructed. PR: Decrease in VP classification. SD: Without PR and PD. PD: Increase in VP classification.	Up to approximately 2 years
Disease control rate(DCR) per RESCIST 1.1	The DCR is defined as the proportion of patients with a documented complete response(CR), partial response(PR) or stable disease(SD) per RECIST 1.1.	Up to approximately 2 years
DCR per mRECIST	The DCR is defined as the proportion of patients with a documented complete response(CR), partial response(PR) or stable disease(SD) per mRECIST.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Haibo Shao
• Collaborators: First Hospital of China Medical University; The Affiliated Hospital of Yanbian University; Liaoning Cancer Hospital & Institute; Harbin Medical University Third Affiliated Hospital; The General Hospital of Northern Theater Command
• Investigators: Principal Investigator: Haibo Shao, First Hospital of China Medical University; Principal Investigator: Tao Han, First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; Donafenib; hepatic arterial infusion chemotherapy; Tislelizumab; HCC - Hepatocellular Carcinoma
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Metabolic Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Glucose Metabolism Disorders; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Nutritional and Metabolic Diseases; Carcinoma, Hepatocellular; Diabetes Mellitus; tislelizumab; donafenib; epalrestat
• Other Study ID Numbers: kelunshen【2025】2025-861-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Consent and privacy: Participants usually only agreed to data use in the original study. Sharing IPD may violate that agreement. And we want to protect our academic credit and avoid misuse of the data.

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.: Yes