Efficacy and Safety of Recombinant Human Adenovirus Type 5 Injection in Combination With TACE-based Combination Therapy in Patients With Stage IIIa Primary Hepatocellular Carcinoma With Portal Vein Thrombosis
Phase: PHASE2
Conditions: Primary Hepatocellular Carcinoma, Portal Vein Thrombosis
Sponsor: Tianjin Medical University Cancer Institute and Hospital

 
 
 
 
Efficacy and safety of recombinant human adenovirus type 5 
injection combined with TACE-based comprehensive 
therapy in patients with primary hepatocellular carcinoma 
with portal vein tumor thrombus in stage IIIa 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version Date: July 18, 2022 

 
Efficacy and safety of recombinant human adenovirus type 5 injection combined with 
TACE-based comprehensive therapy in patients with primary hepatocellular 
carcinoma with portal vein tumor thrombus in stage IIIa 
One、Research purpose and main research content 
Purpose of the study: 
To evaluate and compare the efficacy and safety of recombinant human adenovirus type 
5 injection combined with TACE-based comprehensive therapy in patients with primary 
hepatocellular carcinoma with portal vein tumor thrombus in stage IIIa. 
The main research contents: 
This study is the first to compare the efficacy and safety of recombinant human 
adenovirus type 5 injection via hepatic artery infusion combined with TACE-based 
combination therapy for the treatment of patients with primary hepatocellular carcinoma 
with portal vein carcinoma thrombosis in stage IIIa, providing a safe and reliable treatment 
for the clinical management of this group of patients, as well as a reference and basis for the 
treatment of other tumors with this new treatment modality. 

Two、Research background and basis (research status at home and 
abroad, development trend, necessity, novelty, innovation, research 
significance) 
According to statistics, hepatocellular carcinoma (hereafter referred to as 
hepatocellular carcinoma) accounts for 80% of primary liver cancer worldwide, has a heavy 
disease burden, and is the leading cause of cancer-related deaths in many parts of the world. 
Hepatocellular carcinoma is insidious in origin and develops rapidly, and most patients have 
local progression or distant metastasis by the time they are diagnosed, especially the 
formation of portal vein thrombosis. The incidence of hepatocellular carcinoma with portal 
vein thrombosis is high and the disease progresses rapidly, and the available treatments are 
limited and ineffective. 
It has been found that through palliative treatments such as transarterial 
chemoembolization (TACE) and neoadjuvant three-dimensional conformal radiotherapy, 
some patients can experience regression or even disappearance of portal vein cancer 
thrombus, tumor volume reduction, and disappearance of satellite foci, thus reducing the 
stage of the lesion, increasing the surgical resection rate, and prolonging patient survival. 
TACE is the treatment of choice for unresectable or intermediate to advanced hepatocellular 
carcinoma, which is widely used in clinical practice with positive effects, but the tumor is 
prone to recurrence and metastasis after TACE. Therefore, in most cases, TACE is combined 
with other therapies to treat hepatocellular carcinoma. 
Recombinant human adenovirus type 5 injection (H101) is a structural modification of 
wild-type human type 5 adenovirus, with the deletion of E1B 55KD fragment and E3 partial 
fragment, based on the characteristic that P53 pathway disorder is common to tumors. The 
deletion of E3 fragment enhanced the TNF-induced tumor lysis effect, enhanced the immune 
system's recognition and killing of the virus and infected tumor cells, induced immune 
infiltration, and activated specific anti-tumor immunity, so that the recombinant human 
adenovirus type 5 could play the role of precise tumor lysis and systemic immunity. 
This study is the first to compare the efficacy and safety of recombinant human 

adenovirus type 5 injection via hepatic artery infusion combined with TACE-based 
combination therapy for the treatment of patients with stage IIIa primary hepatocellular 
carcinoma with portal vein carcinoma thrombosis, providing a safe and reliable treatment 
method for the clinical treatment of this group of patients, and also providing a reference and 
basis for the treatment of other tumors with this new treatment model. 

Three、Research methods and technical routes 
Research methods: 
1. Experimental Design 
This is a prospective, single-arm study to evaluate the efficacy and safety of 
recombinant human adenovirus type 5 injection combined with TACE-based combination 
therapy in patients with primary hepatocellular carcinoma with portal vein carcinoma 
thrombosis in stage IIIa. Subjects will be screened and evaluated at the study center, and 
after determining that they meet the inclusion criteria, enrolled patients will be treated with 
recombinant human adenovirus type 5 injection via hepatic artery infusion combined with 
TACE regimen. The study is divided into screening period, baseline period, treatment 
period, and follow-up period. Follow-up after the end of treatment will be every 3 months 
until death or the end of this study. 
2.  Method of administration 
1） Recombinant human adenovirus type 5 injection: Recombinant human adenovirus 
type 5 injection is administered intratumorally 48-72h prior to TACE treatment.Before 
administration, the recombinant human adenovirus type 5 injection was diluted to 30% of 
the total tumor volume with normal saline. H101 dose: 
① The sum of the maximum diameters of the lesions was ≤10cm, and the total dose 
was 1. 0×1012vp (2 injections); 
② The sum of the maximum diameters of the lesions was ＞10cm, and the total dose 
was 1. 5×1012vp (3 injections); 
2）TACE：According to Seldinger technique percutaneous femoral artery puncture, 
arteriogram to determine the tumor location, number, size, distribution range and blood 
supply, microcatheter selectively inserted into the tumor blood supply artery, then slowly 
injected iodinated oil + chemical drugs fully mixed with emulsion. The specific 
chemotherapeutic drugs were: oxaliplatin 85mg/m2, calcium folinic acid 400mg/m2, 
5-fluorouracil 1200mg/m2, and then super liquid iodinated oil embolization was given 
according to the intraoperative imaging tumor blood supply. 

Recombinant human adenovirus type 5 was administered in combination with TACE in 
cycles of every 3 weeks for a total of 2-4 cycles. If patients experience serious adverse 
reactions during this period they need to discontinue the drug. 
Technical route：  
 
图1 技术路线图 
The admittance criteria of the research object 
1. Inclusion Criteria: 
The following criteria must all be met to be included: 
1) Age ≥ 18 years and ≤ 75 years, regardless of gender; 
2) Patients with stage IIIa primary liver cancer diagnosed by histology or imaging; 
3) ECOG physical status score of 0-1; 

4) Expected survival time ≥ 3 months; 
5) Received no liver protective and supportive treatment within two weeks before 
enrollment, and met the following conditions: 
• 
White blood cell count ≥3.0×109/L, neutrophil absolute value ≥3.0×109/L, 
platelet count ≥50×109/L, hemoglobin > 100g/L; 
• 
INR≤1.5 and APTT≤1.5 upper limit of normal or partial prothrombin time 
(PTT) ≤1.5 upper limit of normal;  
• 
 Total bilirubin (TBIL) ≤2.5 times the upper limit of normal value; ALT and 
AST≤5 times the upper limit of normal value; Serum creatinine ≤1.5 times the 
upper limit of normal value;  
• 
Creatinine clearance ≥50ml/min. 
6) Voluntary participation in this study and signing of the informed consent form; 
7) Female patients of childbearing age or male patients whose sexual partners are 
women of childbearing age are required to use effective contraception throughout 
the treatment period and for 6 months after the last dose. 
2. Exclusion Criteria: 
Any of the following circumstances shall be excluded and shall not be selected: 
1）Pregnant or lactating women, men or women who do not wish to use effective 
contraception; 
2) Patients who have received previous treatment with lysoviruses (e.g., T-VEC), 
interventional therapy, or TACE; 
3) Those who are being treated with antiviral drugs; 
4) having received any other experimental drug, antimicrobial drug, or participated in 
another interventional clinical trial within 4 weeks prior to enrollment  
5) Those with a known allergy to the study drug or its active ingredient, or a history of 
allergy to similar biological agents 
6) Evidence of Child-Pugh C hepatic function or hepatocellular dysregulation, including 
those with refractory ascites, ruptured esophageal or gastric variceal bleeding, and 
hepatic encephalopathy 

7) presence of a history of immunodeficiency or autoimmune disease or long-term 
systemic steroid therapy or any form of immunosuppressive therapy within 7 days 
prior to enrollment 
8) With any unstable systemic disease, including but not limited to: severe infection, 
hypertensive patients, uncontrolled diabetes mellitus, unstable angina pectoris, 
cerebrovascular accident or transient cerebral ischemia, abnormal mental status or 
active cerebral hemorrhage, myocardial infarction, congestive heart failure, severe 
arrhythmias requiring drug therapy, renal or metabolic disease, severe hepatic 
dysfunction (including severe jaundice, hepatic encephalopathy, refractory ascites or 
hepatorenal syndrome), multiple organ failure with renal dysfunction; 
9) Previous or concurrent other malignancies; 
10) Combined medical contraindications that preclude any contrast-enhanced imaging 
(CT or MRI); 
11) Other conditions that, in the judgment of the investigator, make the patient 
unsuitable for participation in this study. 
Four、Expected goals, prospects for application of results, social 
benefits 
The project is expected to achieve the following results: 
1) Treatment of patients with stage IIIa primary hepatocellular carcinoma with portal 
vein carcinoma thrombosis using recombinant human adenovirus type 5 injection 
combined with TACE-based combination therapy to improve the objective 
remission rate and provide clinical benefit to patients; 
2) The use of recombinant human adenovirus type 5 injection combined with 
TACE-based combination therapy for the treatment of patients with stage IIIa 
primary hepatocellular carcinoma with portal vein carcinoma thrombosis reduces 
the incidence of adverse effects and results in better clinical safety for patients; 
3) This study is expected to provide a new approach to the clinical treatment of 
hepatocellular carcinoma and provide a reference and basis for the treatment of 
other tumors.