A RCT of TNF and ENT in the Treatment of Long-term Prognosis With Hepatitis B-related HCC After Curative Resection

A Prospective Randomized Controlled Trial of Tenofovir and Entecavir in the Treatment of Long-term Prognosis in Patients With Hepatitis B-related Hepatocellular Carcinoma After Curative Resection

This study evaluates the addition of Tenofovir and Entecavir in the treatment of Hepatitis B-related hepatocellular carcinoma after curative resection in adults. Half of participants will receive Tenofovir disoproxil fumarate, while the other half will receive Entecavir.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma Recurrent
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate 300mg; Drug: Entecavir 0.5 mg

Detailed Description

Antiviral potency significantly differs among various antiviral agents，Entecavir and tenofovir disoproxil fumarate are equally recommendedas first-line treatments for patients with chronic hepatitis B (CHB). However, it is unclear whether treatment with these drugs is associated with equivalent clinical outcomes,especially impacts the risk of HCC recurrence. Entecavir and tenofovir disoproxil fumarate have comparable efficacy in achieving surrogate end points, including virologic response,but they do by different mechanisms .

Entecavir, a guanosine nucleoside analogue with activity against HBV reverse transcriptase (rt),is efficiently phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate functionally inhibits all three activities of the HBV reverse transcriptase: (1) basepriming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA,and (3) synthesis of the positive strand of HBV DNA.

Tenofovir fumarate is a cyclic nucleoside phosphine diester structural analog of adenosine monophosphate. Tenofovir disoproxil fumarate first needs to be converted to tenofovir by hydrolysis of the diester, followed by phosphorylation of cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate competes with the natural substrate 5'-deoxyadenosine triphosphate for its involvement in the synthesis of viral DNA, which, after entering the viral DNA strand, can cause DNA elongation to be blocked due to its lack of 3'-OH groups,thereby blocking the replication of the virus. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerase alpha, beta and mitochondrial DNA polymerase gamma.

• Study Type: Interventional
• Enrollment (Anticipated): 706
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Li Xu; Phone Number: 86-20-87343115; Email: zhouzhg@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhongguo Zhou; Email: zhouzhg@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age 18 to 70 years
2. Positive test for hepatitis B surface antigen (HBsAg) and negative tests for antibodies to hepatitis C virus (HCV-Ab) or to human immunodeficiency virus
3. Clinical diagnosis is consistent with HCC and histopathological result of the resected specimens being HCC
4. No previous treatment of HCC and no previous treatment of hepatitis B with nucleoside or nucleotide analogues or both; no previous treatment with interferon or other immunomodulators
5. BCLC stage 0, A or a solitary tumor with a diameter >5cm
6. No extrahepatic metastasisc
7. No radiologic evidence of invasion into major portal/hepatic venous branches
8. Good liver function with Child-Pugh Class A or Child - Pugh Class B (If B Child - Pugh score ≤7 ) and baseline serum alanine aminotransferase (ALT) level less than 3 times the upper limit of normal (reference range <40IU/L), with no history of encephalopathy, ascites refractory to diuretics, esophagogastric variceal bleeding
9. Good renal function (a serum creatinine level<133mmol/L)
10. Negative resection margin (R0 resection)
11. Laboratory blood tests : WBC≥≥3.0×10^9/L ; PLT≥75×10^9/L ; Hb≥100g/L Cr<133mmol/L ; ALT≤ 150U/L ; AST ≤ 120U/L ; ALB≥30g/L ; TBIL≤34mmol/L INR < 1.5 ; APTT < 18 S

Exclusion Criteria:

1. Eligible patients were excluded if they refused to participate
2. Histopathological result of the resected specimens being not HCC
3. History of antiviral therapy
4. History of receive treatment of HCC， include drugs 、radiofrequency ablation transcatheter arterial chemoembolization or resection
5. age﹤ 18 or ﹥70 years
6. Pregnant or lactating women
7. Poor liver function and poor renal function
8. Suffering from other serious acute or chronic physical or mental illness
9. The following occurred before the study began：Myocardial infarction、 Unstable angina、Coronary artery bypass surgery、Cerebrovascular 、 Pulmonary embolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group A; drugs：tenofovir disoproxil fumarate, dose：300mg/d	Drug: Tenofovir disoproxil fumarate 300mg; Take the medicine once a day ，300mg/d; Other Names: Fu Ma Suan Ti Nuo Fu Wei Er Bi Fu Zhi Pian
Active Comparator: group B; drugs：entecavir dose： 0.5 mg/d	Drug: Entecavir 0.5 mg; Take the medicine once a day，0.5 mg/d; Other Names: EnTiKaWeiPian(BoLuDing)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of HCC	radiologic evidence of tumor recurrence（CT or MRI ） at any time during the following time after liver resection	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of overall patients	36 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2019
• Primary Completion (Anticipated): July 25, 2021
• Study Completion (Anticipated): July 25, 2024

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: antiviral therapy; hepatocellular carcinoma; prognosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Liver Neoplasms; Hepatitis; Carcinoma; Hepatitis B; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir
• Other Study ID Numbers: B2019-05201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No