Anti-angiogenic Targeted Drugs Plus Rg3 to Improve the Efficacy of TACE for Unresectable Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Multicentre Randomized Controlled Study of Anti-angiogenic Targeted Drugs Combined With Ginsenoside Rg3 to Improve the Efficacy of Transcatheter Arterial Chemoembolization (TACE) in the Treatment of Unresectable Hepatocellular Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04523467
• Other study ID #: EHBHKY2020-K-009
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 1, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2020
• Source: Eastern Hepatobiliary Surgery Hospital
• Contact: Feng Shen, MD
• Phone: +862181875005
• Email: shenfengehbh[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with the anti-angiogenic targeted drugs and ginsenoside Rg3 versus TACE alone in patients with unresectable Barcelona Clinic Liver Cancer (BCLC) stage B/C hepatocellular carcinoma (HCC), who has normal liver function and no extrahepatic metastasis.

Description:

TACE is widely used in patients with unresectable HCC, which has been proved to significantly improve the survival time by the results from some randomized controlled studies and meta-analyses. However, due to the different blood supply characteristics and biological heterogeneity in HCC nodules, the therapeutic effect of TACE is limited, and which is still considered as a non-radical treatment. Furthermore, vascular embolization by TACE may result in hypoxia in tumor tissue, which will induce increased secretion of angiogenic factors such as vascular endothelial growth factor (VEGF) and tumor angiogenesis, promote proliferation of residual tumor cells, and enhance tumor invasive and metastasis. Accordingly, the effectiveness of TACE is still unsatisfying as a single treatment for HCC.

Both anti-angiogenic targeted drugs and ginsenoside Rg3 have showed synergistic effect with TACE in patients with unresectable HCC. The purpose of this trial is to evaluate the efficacy and safety of the combination of anti-angiogenic targeted drugs and ginsenoside Rg3 plus TACE comparing to TACE alone in patients with unresectable HCC.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 320
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Aged 18-75

2. Unresectable HCC patients clinically diagnosed or confirmed by histopathology and/or cytology according to Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 edition);

3. At least one measurable lesion (according to mRECIST);

4. BCLC stage B or C (China Liver Cancer Staging [CNLC] IIa, IIb and IIIa);

5. The maximum diameter of a single lesion =10cm; No more than 10 lesions; or combined with portal vein thrombus (PVTT) type I and II (Cheng's classification);

6. Child-pugh score <7;

7. Eastern Cooperative Oncology Group (ECOG) PS 0-1;

Exclusion Criteria:

1. Mixed hepatocellular carcinoma and intrahepatic cholangiocarcinoma (HCC-ICC) confirmed by pathology;

2. Extrahepatic metastasis;

3. Previously received hepatectomy, liver transplantation, interventional therapy, ablative therapy and other local therapies for HCC;

4. PVTT type III/IV (Cheng's classification), major hepatic vein invasion or primary to secondary bile duct invasion;

5. A history of gastrointestinal bleeding or a definite tendency of gastrointestinal bleeding in the past 4 weeks;

6. Cardiovascular diseases with significant clinical significance;

7. Active infection;

8. Other significant clinical and laboratory abnormalities that investigators believe affect safety evaluation.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Anti-angiogenic Targeted Drugs
A tyrosine kinase inhibitor inhibits vascular endothelial growth factor (VEGF) receptors 1-3, showed efficacy in hepatocellular carcinoma
• Ginsenoside Rg3
An active ingredient extracted from ginseng leachate, which can restrain angiogenesis and reduce the expression of programmed cell death ligand 1 (PD-L1) on the tumor cell surface and block the binding of programmed cell death 1 (PD-1) and PD-L1

Procedure:
• TACE
A specific type of chemoembolization that blocks the hepatic artery to treat liver cancer

Locations

Country	Name	City	State
China	Eastern hepatobilliary surgery hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Eastern Hepatobiliary Surgery Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Conversion rate	The proportion of patients whose tumor has changed from unresectable to resectable after Intervention	Up to 2 years
Primary	Progression-free survival (PFS)	the time from randomization to documented progression	Up to 2 years
Secondary	Time to TACE untreated progression	the time from randomization to TACE untreatable progression	Up to 2 years
Secondary	Objective response rate	The proportion of patients whose tumor volume has decreased to a predetermined value	Up to 2 years
Secondary	Overall survival	The time period from the randomization of the patient to the death event due to any reason	Up to 2 years
Secondary	Adverse events	The severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard the severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard the severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard	Up to 2 years