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

Primary Purpose

Hepatocellular Carcinoma Recurrent

Status

Recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Tenofovir disoproxil fumarate 300mg

Entecavir 0.5 mg

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma Recurrent focused on measuring antiviral therapy; hepatocellular carcinoma; prognosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

age 18 to 70 years
Positive test for hepatitis B surface antigen (HBsAg) and negative tests for antibodies to hepatitis C virus (HCV-Ab) or to human immunodeficiency virus
Clinical diagnosis is consistent with HCC and histopathological result of the resected specimens being HCC
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
BCLC stage 0, A or a solitary tumor with a diameter >5cm
No extrahepatic metastasisc
No radiologic evidence of invasion into major portal/hepatic venous branches
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
Good renal function (a serum creatinine level<133mmol/L)
Negative resection margin (R0 resection)
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:

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

Sites / Locations

Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

group A

group B

Arm Description

drugs：tenofovir disoproxil fumarate, dose：300mg/d

drugs：entecavir dose： 0.5 mg/d

Outcomes

Primary Outcome Measures

Recurrence of HCC

radiologic evidence of tumor recurrence（CT or MRI ） at any time during the following time after liver resection

Secondary Outcome Measures

The number of overall patients

Full Information

NCT ID

NCT04392700

First Posted

May 14, 2020

Last Updated

May 18, 2020

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT04392700

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Recruiting

Study Start Date

July 25, 2019 (Actual)

Primary Completion Date

July 25, 2021 (Anticipated)

Study Completion Date

July 25, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma Recurrent

Keywords

antiviral therapy; hepatocellular carcinoma; prognosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

706 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

group A

Arm Type

Experimental

Arm Description

drugs：tenofovir disoproxil fumarate, dose：300mg/d

Arm Title

group B

Arm Type

Active Comparator

Arm Description

drugs：entecavir dose： 0.5 mg/d

Intervention Type

Drug

Intervention Name(s)

Tenofovir disoproxil fumarate 300mg

Other Intervention Name(s)

Fu Ma Suan Ti Nuo Fu Wei Er Bi Fu Zhi Pian

Intervention Description

Take the medicine once a day ，300mg/d

Intervention Type

Drug

Intervention Name(s)

Entecavir 0.5 mg

Other Intervention Name(s)

EnTiKaWeiPian(BoLuDing)

Intervention Description

Take the medicine once a day，0.5 mg/d

Primary Outcome Measure Information:

Title

Recurrence of HCC

Description

radiologic evidence of tumor recurrence（CT or MRI ） at any time during the following time after liver resection

Time Frame

36 months

Secondary Outcome Measure Information:

Title

The number of overall patients

Time Frame

36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: age 18 to 70 years Positive test for hepatitis B surface antigen (HBsAg) and negative tests for antibodies to hepatitis C virus (HCV-Ab) or to human immunodeficiency virus Clinical diagnosis is consistent with HCC and histopathological result of the resected specimens being HCC 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 BCLC stage 0, A or a solitary tumor with a diameter >5cm No extrahepatic metastasisc No radiologic evidence of invasion into major portal/hepatic venous branches 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 Good renal function (a serum creatinine level<133mmol/L) Negative resection margin (R0 resection) 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: Eligible patients were excluded if they refused to participate Histopathological result of the resected specimens being not HCC History of antiviral therapy History of receive treatment of HCC， include drugs 、radiofrequency ablation transcatheter arterial chemoembolization or resection age﹤ 18 or ﹥70 years Pregnant or lactating women Poor liver function and poor renal function Suffering from other serious acute or chronic physical or mental illness The following occurred before the study began：Myocardial infarction、 Unstable angina、Coronary artery bypass surgery、Cerebrovascular 、 Pulmonary embolism

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Li Xu

Phone

86-20-87343115

zhouzhg@sysucc.org.cn

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zhongguo Zhou

zhouzhg@sysucc.org.cn

12. IPD Sharing Statement

Learn more about this trial

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

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