Effect and Safety of Recombinant Human Adenovirus Type 5 in Advanced HCC With Stable Disease After Sorafenib Treatment

Hepatocellular Carcinoma Clinical Trial

Official title: Effect and Safety of Recombinant Human Adenovirus Type 5 (H101) in Advanced Hepatocellular Carcinoma Patients With Stable Disease After Sorafenib Treatment: A Randomized, Parallel-Controlled Clinical Trial

Status Active, not recruiting

Clinical Trial Summary

Sorafenib, as a first-line treatment for patients with advanced HCC, can significantly prolong the overall survival rate of patients. However, about 53-71% of patients showed stable disease (SD) after sorafenib treatment, and further studies to explore optimal therapy for these patients are still needed.

Oncolytic viruses are a type of virus that can selectively replicate in tumor cells and then destroy tumor cells, of which recombinant human adenovirus type 5 (H101) is the first oncolytic virus drug which was approved in the world. Recent studies indicate that H101 shows anti-tumor effects on liver cancer and there may be a synergistic effect between recombinant human adenovirus type 5 and sorafenib in the inhabitation of hepatoma cells in vitro. This study aims to further verify the effect and safety of recombinant human adenovirus type 5 combined with sorafenib in the treatment of advanced hepatocellular carcinoma.

Clinical Trial Description

Primary liver cancer is the fourth most common malignant tumor and the second most lethal cause of tumor in China, mainly including Hepatocellular carcinoma (HCC) and Intrahepatic Cholangiocarcinoma. ICC) and HCC-ICC, among which hepatocellular carcinoma accounts for about 75% of all primary liver cancer, bringing a heavy disease burden to China's health system and society. At present, for patients with unresectable advanced liver cancer, the commonly used treatment options include transcatheter chemoembolization (TACE), systemic therapy and radiotherapy. Since the introduction of the molecular-targeted drug Sorafenib in 2007, a number of clinical studies have shown that sorafenib has benefits for patients with advanced liver cancer in different countries and regions and with different liver disease backgrounds. It has become the standard therapy for advanced HCC and has been recommended for first-line treatment of advanced HCC patients by guidelines of many countries. However, although sorafenib can significantly prolong the overall survival rate, about 53-71% of patients still show stable disease (SD) after treatment. For these patients, further exploration is needed to optimize the treatment.

Oncolytic viruses are a class of viruses that can selectively replicate in tumor cells and then lytic tumor cells. Among them, recombinant human adenovirus TYPE 5 H101 is the world's first commercially available oncolytic drug, which has been approved for the treatment of head and neck tumors in 2003. Recombinant human adenovirus type 5 (H101) is a kind of oncolytic adenovirus, which can selectively replicate in tumor cells with deficient tumor suppressor gene p53 by knocking out e1B-55KD gene and partial gene fragment (78.3 ~ 85.8μm) of E3 region of human adenovirus type 5. Based on the data from the head and neck tumor-related clinical trial of recombinant human adenovirus H101, the drug has been approved for the treatment of advanced nasopharyngeal carcinoma in China. Based the study found that in recent years, in addition to the head and neck cancer, human recombinant adenovirus type 5 H101 also displayed antitumor effect on liver cancer, and the selective killing effect of the low concentration H101 on liver cancer cell associated with p53 gene mutation, and the high concentration of H101 on liver cancer cell and immortalized the role of normal liver cells is not restricted by cell p53 status. In vitro studies showed that both H101 and sorafenib alone could significantly inhibit the proliferation and induce apoptosis of human hepatoma cell lines HepG2 and Hep3B, and the combined effect of the two drugs was more significant than that of single drug 16. The synergistic mechanism of recombinant adenovirus H101 and sorafenib may be related to the influence of Raf/MEK/ERK signaling pathway. Sorafenib can block Raf/MEK/ERK signal transduction pathway, thereby inhibiting angiogenesis, while down-regulating the expression level of anti-apoptotic protein McL-1, and further inducing apoptosis of tumor cells. Meanwhile, sorafenib can upregulate the expression of Coxsackie adenovirus receptor (CAR) on the surface of hepatocellular carcinoma cells, increase the sensitivity of tumor cells to adenovirus, and enhance the oncolytic effect of H101. In addition, H101 combined with sorafenib can also effectively inhibit the expression of VEGF, thereby inhibiting the proliferation of tumor cells.

Based on the human recombinant adenovirus type 5 show the joint sorafenib synergy and its potential for the curative effect of hepatocellular carcinoma, this research intends to carry out a prospectie, intrusive, single-arm study, further validation of human recombinant adenovirus type 5 joint sorafenib therapy efficacy and safety of primary liver cancer, provides evidence-based medical evidence to support for clinical medication. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

• NCT number: NCT05113290
• Study type: Interventional
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 28, 2021
• Completion date: December 1, 2023