HCC Patients After Curative Treatment With Low HBV Viral LoadPhase 4NCT04290936
Tenofovir Alafenamide(TAF) Reduces the Risk of Hepatocellular Carcinoma(HCC) Recurrence
A Phase 4 study testing Vemlidy® (Tenofovir Alafenamide; TAF) in people with HCC Patients After Curative Treatment With Low HBV Viral Load, run by Taipei Veterans General Hospital, Taiwan at 4 sites in Taiwan.
Trial summary
Hepatocellular carcinoma(HCC) is prevalent in the hepatitis B virus(HBV) infection endemic areas. For early stage of HCC, surgical resection, radiofrequency ablation (RFA) or microwave ablation (MWA) are the main treatment options. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- HCC Patients After Curative Treatment With Low HBV Viral Load
- What is being tested?
- Vemlidy® (Tenofovir Alafenamide; TAF)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 402 participants
- Where
- 4 sitesTaiwan
- Study dates
- 16 Oct 2020to 31 Dec 2024
- Phase
- Phase 4
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HBsAg-positive for more than 6 months.
- HCC after curative treatment (eight by surgical resection or RFA or MWA) with significant liver fibrosis (either by Ishak≧2, Metavir≧2, Knodell≧3) or cirrhosis and HBV DNA<2,000 IU/ml.
- The duration of curative treatment of HCC to study enrollment should be less than 90 days.
- Curative treatment is confirmed by contrast-enhanced CT or MR after the surgery/RFA/MWA.
Who cannot join
- Child-Pugh class B8-C.
- Active EV bleeding within 4 weeks.
- History of hepatic encephalopathy or intractable ascites.
- BCLC C or D.
Trial locations and contacts
4 sites in 1 country.
Taiwan4 sites, 2 recruiting
- Active, not recruiting
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, State..., 807
- Recruiting
National Taiwan University Hospital
Taipei, State..., 100
Chieh-Ju Lee, Master, +886-939859265, ssbugi@gmail.com
Chun-Jen Liu, M.D. Ph.D.
- Active, not recruiting
Tri-Service General Hospital
Taipei, State..., 114
- Recruiting
Taipei Veterans General Hospital
Taipei, 11217
Yi-Hsaing Huang, M.D. Ph.D., +886-2-28757506, yhhuang@vghtpe.gov.tw
Chieh-Ju Lee, Master, +886-939859265, ssbugi@gmail.com
About this study
Official title: Decreasing Risk of Recurrence by TAF in HCC Patients After Curative Treatment With Low HBV Viral Load
Hepatocellular carcinoma(HCC) is prevalent in the hepatitis B virus(HBV) infection endemic areas. For early stage of HCC, surgical resection, radiofrequency ablation (RFA) or microwave ablation (MWA) are the main treatment options. However, the risk of recurrence is as high as 50% in 5 years by surgical resection or 60-70% in 5 years by RFA. In average, the recurrence rate of HCC at 2 years is 30%. Many factors are associated with the HCC recurrence, including HBV viral load, cirrhotic stage, tumor size, tumor number, vascular invasion, alpha-fetoprotein(AFP) level and so on. Of them, high HBV viral load is associated with the risk of HCC recurrence after surgical resection, especially on late recurrence. In one previous randomized controlled trial, patients who received lamivudine, adefovir dipivoxil, or entecavir had significantly decreased early recurrence of HCC, however, whether nucleos(t)ide analogues(NUCs) can further reduce the risk of recurrence in patients with low viral loads (<2000 IU/ml) is still unclear.
In EASL 2017 guideline, all patients with compensated or decompensated cirrhosis need antiviral treatment, with any detectable HBV DNA level and regardless of alanine aminotransferase(ALT) levels. In Taiwan, even in chronic hepatitis B(CHB) infection patients with HCC, NUC is not reimbursed if their HBV viral load was less than 2000 IU/ml. It is an important unmet medical need to understanding the role of TAF in reducing the risk of recurrence in HBV-HCC patients with low HBV viral load (HBV DNA<2000 IU/ml) and significant liver fibrosis after curative treatment (The definition of significant liver fibrosis was based on reference. In our recent retrospective study, the risk of recurrence and survival are comparable between patients with and without NUCs treatment before HCC development only if NUCs treatment can be provided after curative treatment of HCC. However, a higher risk of recurrence was observed in cirrhotic patients with prior NUCs treatment before HCC occurrence. It would be interesting to investigate the incidence of recurrence by switching to tenofovir alafenamide(TAF) after curative treatment of HCC in patients already on NUCs treatment.
- Being tested
- Vemlidy® (Tenofovir Alafenamide; TAF), Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vemlidy® (Tenofovir Alafenamide; TAF)Drug
Dosage form: Oral Tablets; Dosage: 25mg; Frequency: One tablet with meals, once daily(QD).
PlaceboDrug
Dosage form: Oral Tablets; Dosage: N/A; Frequency: One tablet with meals, once daily(QD).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | NUC-naïve patients will be randomization into Tenofovir Alafenamide(TAF) treatment. Receives: Drug: Vemlidy® (Tenofovir Alafenamide; TAF) |
| Arm 2 | Placebo comparator | NUC-naïve patients will be randomization into placebo arm. Receives: Drug: Placebo |
| Arm 3 | Active comparator | NUCs-treated patients will be switched to Tenofovir Alafenamide(TAF) treatment. Receives: Drug: Vemlidy® (Tenofovir Alafenamide; TAF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Hepatocellular carcinoma(HCC) recurrence
Incidence of HCC recurrence
Measured: Up to 2 years.
Secondary outcomes (6)
Hepatocellular carcinoma(HCC) recurrence
HCC recurrence
Measured: Up to 3 years.
Hepatocellular carcinoma(HCC) recurrence in NUCs-treated patients after switched to TAF treatment
HCC recurrence in NUCs-treated patients after switched to TAF treatment
Measured: Up to 2 years.
Dynamic (kinetics) changes in the bio-markers related to hepatitis B virus(HBV) infection
HBV DNA, HBsAg, HBV RNA, HBcrAg, etc.
Measured: Up to 3 years.
Changes in the renal function
eGFR
Measured: Up to 3 years.
Changes in the bone density
Dual-energy X-ray absorptiometry(DEXA) scan
Measured: Up to 3 years.
Regression of liver fibrosis
Fibroscan
Measured: Up to 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2020
- Study start16 Oct 2020
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCC Patients After Curative Treatment With Low HBV Viral LoadStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part 1: NUC-naïve patients will be randomization into tenofovir alafenamide(TAF) or placebo arm in 1:1 ratio. Part 2: NUCs-treated patients will be switched to tenofovir alafenamide(TAF) treatment.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 402 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Responsible party
- Principal investigator, vghtpe user, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04290936
- Sponsor's protocol ID
- IN-TW-320-5598
- Status last verified
- Jul 2021
- First submitted
- 27 Feb 2020
- Last updated
- 9 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decreasing Risk of Recurrence by TAF in HCC Patients After Curative Treatment With Low HBV Viral Load
- ClinicalTrials.gov ID
- NCT04290936
- Acronym / sponsor ID
- IN-TW-320-5598
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 402 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Study start
- 16 Oct 2020 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 2 Mar 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.
Hepatocellular carcinoma(HCC) is prevalent in the hepatitis B virus(HBV) infection endemic areas. For early stage of HCC, surgical resection, radiofrequency ablation (RFA) or microwave ablation (MWA) are the main treatment options. However, the risk of recurrence is as high as 50% in 5 years by surgical resection or 60-70% in 5 years by RFA. In average, the recurrence rate of HCC at 2 years is 30%. Many factors are associated with the HCC recurrence, including HBV viral load, cirrhotic stage, tumor size, tumor number, vascular invasion, alpha-fetoprotein(AFP) level and so on. Of them, high HBV viral load is associated with the risk of HCC recurrence after surgical resection, especially on late recurrence. In one previous randomized controlled trial, patients who received lamivudine, adefovir dipivoxil, or entecavir had significantly decreased early recurrence of HCC, however, whether nucleos(t)ide analogues(NUCs) can further reduce the risk of recurrence in patients with low viral loads (<2000 IU/ml) is still unclear.
In EASL 2017 guideline, all patients with compensated or decompensated cirrhosis need antiviral treatment, with any detectable HBV DNA level and regardless of alanine aminotransferase(ALT) levels. In Taiwan, even in chronic hepatitis B(CHB) infection patients with HCC, NUC is not reimbursed if their HBV viral load was less than 2000 IU/ml. It is an important unmet medical need to understanding the role of TAF in reducing the risk of recurrence in HBV-HCC patients with low HBV viral load (HBV DNA<2000 IU/ml) and significant liver fibrosis after curative treatment (The definition of significant liver fibrosis was based on reference. In our recent retrospective study, the risk of recurrence and survival are comparable between patients with and without NUCs treatment before HCC development only if NUCs treatment can be provided after curative treatment of HCC. However, a higher risk of recurrence was observed in cirrhotic patients with prior NUCs treatment before HCC occurrence. It would be interesting to investigate the incidence of recurrence by switching to tenofovir alafenamide(TAF) after curative treatment of HCC in patients already on NUCs treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Part 1: NUC-naïve patients will be randomization into tenofovir alafenamide(TAF) or placebo arm in 1:1 ratio. Part 2: NUCs-treated patients will be switched to tenofovir alafenamide(TAF) treatment.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Vemlidy® (Tenofovir Alafenamide; TAF)NUC-naïve patients will be randomization into Tenofovir Alafenamide(TAF) treatment. |
| Arm 2 | Placebo comparator | Drug: PlaceboNUC-naïve patients will be randomization into placebo arm. |
| Arm 3 | Active comparator | Drug: Vemlidy® (Tenofovir Alafenamide; TAF)NUCs-treated patients will be switched to Tenofovir Alafenamide(TAF) treatment. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HBsAg-positive for more than 6 months.
- HCC after curative treatment (eight by surgical resection or RFA or MWA) with significant liver fibrosis (either by Ishak≧2, Metavir≧2, Knodell≧3) or cirrhosis and HBV DNA<2,000 IU/ml.
- The duration of curative treatment of HCC to study enrollment should be less than 90 days.
- Curative treatment is confirmed by contrast-enhanced CT or MR after the surgery/RFA/MWA.
Key exclusion criteria (4 listed)
- Child-Pugh class B8-C.
- Active EV bleeding within 4 weeks.
- History of hepatic encephalopathy or intractable ascites.
- BCLC C or D.
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 |
|---|---|---|
| Vemlidy® (Tenofovir Alafenamide; TAF)Dosage form: Oral Tablets; Dosage: 25mg; Frequency: One tablet with meals, once daily(QD). | Drug | Arm 1, Arm 3 |
| PlaceboDosage form: Oral Tablets; Dosage: N/A; Frequency: One tablet with meals, once daily(QD). | Drug | Arm 2 |
Primary outcome
Incidence of Hepatocellular carcinoma(HCC) recurrence
Time frame: Up to 2 years.
Incidence of HCC recurrence
6 secondary outcomes
Hepatocellular carcinoma(HCC) recurrence
Time frame: Up to 3 years.
Hepatocellular carcinoma(HCC) recurrence in NUCs-treated patients after switched to TAF treatment
Time frame: Up to 2 years.
Dynamic (kinetics) changes in the bio-markers related to hepatitis B virus(HBV) infection
Time frame: Up to 3 years.
Changes in the renal function
Time frame: Up to 3 years.
Changes in the bone density
Time frame: Up to 3 years.
Regression of liver fibrosis
Time frame: Up to 3 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
- Individual participant dataSharing planned: No
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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vemlidy® (Tenofovir Alafenamide; TAF) in people with HCC Patients After Curative Treatment With Low HBV Viral Load, run by Taipei Veterans General Hospital, Taiwan at 4 sites in Taiwan.
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 4 inclusion and 4 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 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Taiwan. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Yi-Hsiang Huang, M.D. Ph.D. (+886-2-28757506, yhhuang@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Hepatocellular carcinoma(HCC) recurrence (time frame: Up to 2 years.). 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 9 Jul 2021.