Clinical Trials Logo

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. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT05113290
Study type Interventional
Source First Affiliated Hospital Xi'an Jiaotong University
Contact Chang Liu, MD
Phone 0086-18991232095
Email [email protected]
Status Not yet recruiting
Phase Phase 4
Start date December 1, 2021
Completion date December 1, 2023

See also
  Status Clinical Trial Phase
Recruiting NCT04209491 - Interest of the Intervention of a Nurse Coordinator in Complex Care Pathway
Completed NCT03963206 - Cabozantinib toLERANCE Study in HepatoCellular Carcinoma (CLERANCE) Phase 4
Active, not recruiting NCT05068193 - A Clinical Trial to Compare the Pharmacokinetics and Bioequivalence of "BR2008" With "BR2008-1" in Healthy Volunteers Phase 1
Active, not recruiting NCT03781934 - A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations Phase 1/Phase 2
Active, not recruiting NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT04401800 - Preliminary Antitumor Activity, Safety and Tolerability of Tislelizumab in Combination With Lenvatinib for Hepatocellular Carcinoma Phase 2
Recruiting NCT03746704 - Study of ImmunoPet Imaging of PD-L1 in Tumors Using 89Zr-DFO-REGN3504 in Participants With Advanced PD-L1 Positive Malignancies Phase 1
Recruiting NCT04641637 - Substudy: Interconnection of Arterial Tumor Feeders Through Tumor Sinusoid in HCC N/A
Recruiting NCT04780802 - Balloon Assisted Transarterial Therapy for Hepatocellular Carcinoma N/A
Recruiting NCT04767906 - Cabozantinib Treatment in a Phase II Study for Patients With Hepatocellular Carcinoma (HCC) Refractory to PD-1 Inhibitors Phase 2
Not yet recruiting NCT05044676 - Immune Cells as a New Biomarker of Response in Patients Treated by Immunotherapy for Advanced Hepatocellular Carcinoma
Recruiting NCT03970616 - A Study of Tivozanib in Combination With Durvalumab in Subjects With Advanced Hepatocellular Carcinoma Phase 1/Phase 2
Active, not recruiting NCT04039607 - A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma Phase 3
Recruiting NCT03642561 - Evaluation the Treatment Outcome for RFA in Patients With BCLC Stage B HCC in Comparison With TACE Phase 2/Phase 3
Recruiting NCT04118114 - Phase II Study of PRL3-ZUMAB in Advanced Solid Tumors Phase 2
Active, not recruiting NCT03222076 - Nivolumab With or Without Ipilimumab in Treating Patients With Resectable Liver Cancer Phase 2
Terminated NCT03219372 - Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence Phase 2
Completed NCT01908426 - Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib Phase 3
Not yet recruiting NCT04550663 - NKG2D CAR-T(KD-025) in the Treatment of Relapsed or Refractory NKG2DL+ Tumors Phase 1