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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Anti-angiogenic Targeted Drugs
* Drug: Ginsenoside Rg3
* Procedure: TACE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-75 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); At least one measurable lesion (according to mRECIST); BCLC stage B or C (China Liver Cancer Staging [CNLC] IIa, IIb and IIIa); 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); Child-pugh score <7; Eastern Cooperative Oncology Group (ECOG) PS 0-1; Exclusion Criteria: Mixed hepatocellular carcinoma and intrahepatic cholangiocarcinoma (HCC-ICC) confirmed by pathology; Extrahepatic metastasis; Previously received hepatectomy, liver transplantation, interventional therapy, ablative therapy and other local therapies for HCC; PVTT type III/IV (Cheng's classification), major hepatic vein invasion or primary to secondary bile duct invasion; A history of gastrointestinal bleeding or a definite tendency of gastrointestinal bleeding in the past 4 weeks; Cardiovascular diseases with significant clinical significance; Active infection; Other significant clinical and laboratory abnormalities that investigators believe affect safety evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined group<br>Anti-angiogenic targeted drug + Rg3 + TACE | Drug: Anti-angiogenic Targeted Drugs<br>* A tyrosine kinase inhibitor inhibits vascular endothelial growth factor (VEGF) receptors 1-3, showed efficacy in hepatocellular carcinoma<br>* Other names: TKI Drugs;Drug: Ginsenoside Rg3<br>* 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<br>* Other names: Rg3;Procedure: TACE<br>* A specific type of chemoembolization that blocks the hepatic artery to treat liver cancer<br>|
| Active Comparator: Single group<br>TACE alone | Procedure: TACE<br>* A specific type of chemoembolization that blocks the hepatic artery to treat liver cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | the time from randomization to documented progression | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to TACE untreated progression | the time from randomization to TACE untreatable progression | Up to 2 years | 
| Objective response rate | The proportion of patients whose tumor volume has decreased to a predetermined value | Up to 2 years | 
| Overall survival | The time period from the randomization of the patient to the death event due to any reason | Up to 2 years | 
| 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 |