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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Anti-angiogenic Targeted Drugs; Drug: Ginsenoside Rg3; Procedure: TACE

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feng Shen, MD; Phone Number: +862181875005; Email: shenfengehbh@sina.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200438
      • Eastern hepatobilliary surgery hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion rate	The proportion of patients whose tumor has changed from unresectable to resectable after Intervention	Up to 2 years

Collaborators and Investigators

• Sponsor: Eastern Hepatobiliary Surgery Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2020
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (ACTUAL): August 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 21, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Angiogenesis Inhibitors; Ginsenoside Rg3
• Other Study ID Numbers: EHBHKY2020-K-009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No