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

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07557914

Enrollment

Registered

2026-04-30

Start date

2026-06-01

Completion date

2029-02-01

Last updated

2026-06-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes, HCC - Hepatocellular Carcinoma

Keywords

hepatic arterial infusion chemotherapy, Donafenib, Tislelizumab, HCC - Hepatocellular Carcinoma, Diabetes

Brief summary

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.

Interventions

DRUGEpalrestat

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.

DRUGDonafenib + Tislelizumab

donafenib 0.2g BID, tislelizumab 200mg/21days

PROCEDUREHAIC

Include FOLFOX and RALOX.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
12-month Event-free survival (EFS) Rate	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.	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.)

Secondary

Measure	Time frame	Description
Event-free survival (EFS)	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.	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).
Overall survival (OS)	Up to approximately 2 years	The OS is defined as the time from the enrollment to death due to any cause.
Progression free survival(PFS) (Overall)	From enrollment to progressive disease (according to mRECIST) or death due to any cause, up to 2 years.	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.
Progression free survival(PFS) of intra-hepatic lesions	From the enrollment to the first documented progressive disease of intra-hepatic lesions or death due to any cause, up to 2 years.	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.
Progression free survival(PFS) of extra-hepatic lesions	From the enrollment to the first documented appearance of extra-hepatic lesions or death due to any cause, up to 2 years.	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.
Objective response rate(ORR) per RESCIST 1.1	Up to approximately 2 years	The ORR is defined as the proportion of patients with a documented complete response(CR) or partial response(PR) per RECIST 1.1.
ORR per mRECIST	Up to approximately 2 years	The ORR is defined as the proportion of patients with a documented CR or PR per mRECIST.
PVTT response rate per mRECIST	Up to approximately 2 years	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.
Disease control rate(DCR) per RESCIST 1.1	Up to approximately 2 years	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.
DCR per mRECIST	Up to approximately 2 years	The DCR is defined as the proportion of patients with a documented complete response(CR), partial response(PR) or stable disease(SD) per mRECIST.
Adverse event(AE) per Common Terminology Criteria for Adverse Events(CTCAE) 5.0	Up to approximately 2 years	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.

Countries

China

Contacts

CONTACTHongbin Zou

hongbinzou300@gmail.com+8618040026871

PRINCIPAL_INVESTIGATORHaibo Shao

First Hospital of China Medical University

PRINCIPAL_INVESTIGATORTao Han