Donafenib Plus Sintilimab for Advanced HCC

Donafenib Combined with Sintilimab for Advanced HCC: a Single-arm, Single-center, Prospective Study

This study will evaluate the efficacy and safety of donafenib combined with sintilimab in patients with advanced hepatocellullar carcinoma (HCC).

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Donafenib+sintilimab

Detailed Description

This is a Phase II study to evaluate the efficacy and safety of donafenib combined with sintilimab in patients with advanced HCC.

30 subjects with advanced HCC (Barcelona-Clinic- Liver-Cancer [BCLC] stage C, or China liver cancer staging [CNLC] IIIa/IIIb) will be enrolled in the study.

Part 1 (Safety Run-in): 6 patients will receive donafenib 200mg P.O. BID and sintilimab 200mg I.V. for a 21-day cycle.

Part 2: patients will receive donafenib at the recommended phase 2 dose determined from Part 1 and sintilimab 200mg I.V. Q3W.

Donafenib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sintilimab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Patients will be allowed to have donafenib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • The second Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Advanced HCC (BCLC stage C or CNLC IIIa/IIIb ) with diagnosis confirmed by histology/cytology or clinically
• Patients who have Tumor recurrence after surgical resection or ablation are allowed to be included
• Patients who previously received local treatment, such as transcatheter arterial chemoembolization, transcatheter arterial embolization and radiotherapy, are allowed to be included
• At least one measurable lesion
• Child-Pugh score ≤7
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and hematologic function
• Life expectancy of at least 3 months

Exclusion Criteria:

• Diffuse HCC
• Macrovascular invasion involving the main trunk or inferior vena cava
• Central nervous system metastasis
• History of malignancy other than HCC
• Esophageal and/or gastric varices bleeding within 3 months prior to initiation of study treatment
• Uncontrolled ascites
• History of hepatic encephalopathy
• Patients who received prior systemic therapy (chemotherapy, targeted therapy or immunotherapy) or hepatic arterial infusion chemotherapy (HAIC) for HCC
• History of organ and cell transplantation
• Active severe infection; use of antibiotics within 2 weeks prior to injection of sintilimab
• Autoimmune disease or immune deficiency
• Severe organ (heart, kidney) dysfunction

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: Donafenib+sintilimab; Donafenib combined with sitilimab.

Drug: Donafenib+sintilimab; Part 1 (Safety Run-in): donafenib 200mg P.O. BID and sintilimab 200mg I.V. for a 21-days cycle. Part 2: donafenib at the recommended phase 2 dose determined from Part 1 and sintilimab 200mg I.V. Q3W. Donafenib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sintilimab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Patients will be allowed to have donafenib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) assessed by investigators according to modified Response Evalutaion Criteria in Solid Tumors (mRECIST).	The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), AE of special interest (AESI), serious adverse event (SAE), assessed by NCI CTCAE v5.0.	18 months
PFS assessed by investigators according to Response Evalutaion Criteria in Solid Tumors (RECIST) v1.1	The time from initiation of treatment until the first occurrence of disease progression or death from any cause, whichever occurs first.	18 months
Objective response rate (ORR) assessed by investigators according to mRECIST.	The percentage of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR).	18 months
Disease control rate (DCR) assessed by investigators according to mRECIST.	The percentage of patients who had a tumor response rating of CR, PR, or stable disease (SD).	18 months
ORR assessed by investigators according to RECIST 1.1.	The percentage of patients who had a best overall tumor response rating of CR or PR.	18 months
DCR assessed by investigators according to RECIST 1.1.	The percentage of patients who had a tumor response rating of CR, PR, or SD.	18 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Guangzhou Medical University
• Investigators: Principal Investigator: Kangshun Zhu, Dr., Second Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2021
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 4, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Donafenib; Sintilimab; PD-1 inhibitor; TKI
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: MIIR-08

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