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

Phase 3

• Conditions: Hepatocellular Carcinoma Recurrent
• Interventions: Drug: Tenofovir disoproxil fumarate 300mg; Drug: Entecavir 0.5 mg

• Registration Number: NCT04392700
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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.

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 Timeline

• Study Start: 2019-07-25
• Status Verified: 2020-05
• Study First Submitted: 2020-05-14
• Study First Submitted QC: 2020-05-18
• Last Update Submitted: 2020-05-18
• Study First Posted: 2020-05-19
• Last Update Posted: 2020-05-19
• Primary Completion: 2021-07-25
• Study Completion: 2024-07-25

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 706

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
group A	Tenofovir disoproxil fumarate 300mg	drugs：tenofovir disoproxil fumarate, dose：300mg/d
group B	Entecavir 0.5 mg	drugs：entecavir dose： 0.5 mg/d

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
The number of overall patients	36 months

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China