Hepatocellular Carcinoma RecurrentPhase 3NCT04392700
A RCT of TNF and ENT in the Treatment of Long-term Prognosis With Hepatitis B-related HCC After Curative Resection
A Phase 3 study testing Tenofovir disoproxil fumarate 300mg and Entecavir 0.5 mg in people with Hepatocellular Carcinoma Recurrent, run by Sun Yat-sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma Recurrent
- What is being tested?
- Tenofovir disoproxil fumarate 300mg and Entecavir 0.5 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 706 participants
- Where
- 1 siteChina
- Study dates
- 25 Jul 2019to 25 Jul 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Zhongguo Zhou, zhouzhg@sysucc.org.cn
About this study
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
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.
Read the 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.
- Conditions
- Hepatocellular Carcinoma Recurrent
- Being tested
- Tenofovir disoproxil fumarate 300mg, Entecavir 0.5 mg
- Keywords
- antiviral therapy; hepatocellular carcinoma; prognosis
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir disoproxil fumarate 300mgDrug
Also called Fu Ma Suan Ti Nuo Fu Wei Er Bi Fu Zhi Pian
Take the medicine once a day ，300mg/d
Entecavir 0.5 mgDrug
Also called EnTiKaWeiPian(BoLuDing)
Take the medicine once a day，0.5 mg/d
| Study group | Role | What they receive |
|---|---|---|
| group A | Experimental | drugs：tenofovir disoproxil fumarate, dose：300mg/d Receives: Drug: Tenofovir disoproxil fumarate 300mg |
| group B | Active comparator | drugs：entecavir dose： 0.5 mg/d Receives: Drug: Entecavir 0.5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of HCC
radiologic evidence of tumor recurrence（CT or MRI ） at any time during the following time after liver resection
Measured: 36 months
Secondary outcomes (1)
The number of overall patients
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2020
- Study start25 Jul 2019
- Primary completion25 Jul 2021 (estimated)
- Study completion25 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma RecurrentStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 706 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhongguo Zhou, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04392700
- Sponsor's protocol ID
- B2019-05201
- Status last verified
- May 2020
- First submitted
- 14 May 2020
- Last updated
- 19 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04392700
- Acronym / sponsor ID
- B2019-05201
- Conditions
- Hepatocellular Carcinoma Recurrent
- Keywords
- antiviral therapy; hepatocellular carcinoma; prognosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 706 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 25 Jul 2019 (actual)
- Primary completion
- 25 Jul 2021 (estimated)
- Study completion
- 25 Jul 2024 (estimated)
- First posted
- 19 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group A | Experimental | Drug: Tenofovir disoproxil fumarate 300mgdrugs：tenofovir disoproxil fumarate, dose：300mg/d |
| group B | Active comparator | Drug: Entecavir 0.5 mgdrugs：entecavir dose： 0.5 mg/d |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir disoproxil fumarate 300mgAlso: Fu Ma Suan Ti Nuo Fu Wei Er Bi Fu Zhi PianTake the medicine once a day ，300mg/d | Drug | group A |
| Entecavir 0.5 mgAlso: EnTiKaWeiPian(BoLuDing)Take the medicine once a day，0.5 mg/d | Drug | group B |
Primary outcome
Recurrence of HCC
Time frame: 36 months
radiologic evidence of tumor recurrence（CT or MRI ） at any time during the following time after liver resection
1 secondary outcome
The number of overall patients
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenofovir disoproxil fumarate 300mg and Entecavir 0.5 mg in people with Hepatocellular Carcinoma Recurrent, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Li Xu (86-20-87343115, zhouzhg@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence of HCC (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2020.