Donafenib Plus Sintilimab for Advanced HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05162352
• Other study ID #: MIIR-08
• Status: Recruiting
• Phase: Phase 2
• Start date: December 4, 2021
• Est. completion date: May 2023

Study information

• Verified date: December 2021
• Source: Second Affiliated Hospital of Guangzhou Medical University
• Contact: Mingyue Cai, Dr.
• Phone: +86-20-34156205
• Email: cai020[@]yeah.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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