Hepatocellular CarcinomaPhase 4NCT02959359
DAA in the Risk of Recurrence After Curative Treatment of HCC
A Phase 4 study testing Ledipasvir 90mg/Sofosbuvir 400 mg and Ribavirin in people with Hepatocellular Carcinoma, run by Taipei Veterans General Hospital, Taiwan.
Trial summary
For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Ledipasvir 90mg/Sofosbuvir 400 mg and Ribavirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2016to Dec 2022
- 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
- Anti-HCV positive and HBsAg-negative
- HCV genotype 1 or 2 infection, mixed infection GT 1 \& 2 is allowed
- HCV RNA ≥ 10,000 IU/ml at the time of screening
- Age > 20 y/o
- BCLC stage 0 or A HCC confirmed by pathology and receiving the first time of curative treatment
- No recurrence of HCC confirmed by contrast-enhanced image studies (CT or MRI) within 3 months post the curative treatment.
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
- Child-Pugh score ≤7
Who cannot join
- HBV, or HIV coinfection
- Co-existing other malignancy
- Intolerance to ribavirin
- Marked decompensated liver cirrhosis (CTP score>7)
- Uremia or renal impaired patients (eGFR<30)
About this study
Official title: The Role of DAA in Reducing the Risk of Recurrence After Curative Treatment of HCC in Patients With Chronic Hepatitis C and Early Stage HCC
For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. Only selected patients are eligible and tolerable to IFN-based treatment after surgical resection and the sustained virological response varied.
Harvoni for genotype 1 HCV and sovaldi plus ribavirin for genotype 2 HCV can achieve high SVR and being recommended by AASLD and EASL. Mixed HCV genotype infection accounts for 10% of CHC patients in Taiwan. Sovaldi-based treatment plus ribavirin should be as effective as Sovaldi plus rivavirin in the treatment of genotype 2 HCV, as well as mixed genotype 1 and 2 HCV infection. As genotype 1 and 2 are the leading HCV genotypes in Taiwan, It can simplify the regimen of anti-HCV treatment in Taiwan by using Harvoni plus ribavirin, not only for genotype 1 and 2 HCV but also for mixed genotype 1 and 2 HCV infection. Although an unexpected high recurrence rate in HCC patients under DAA treatment was reported once. However, one recent study showed a low risk of HCC recurrence after DAA treatment. In this study, the investigators plan to enroll 130 HCV-HCC patients after confirming curative treatment for their HCC, either by surgery or RFA. For the cases fulfilling the inclusion/exclusion criteria, a 12 weeks Harvoni plus ribavirin treatment will be provided for all cases (single armed design). The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. A hospital-based cohorts of HCV-related HCC undergoing surgical resection or RFA from Taipei Veterans General Hospital and Investigated Sites will be recruited as historical controls.
Read the detailed description
Chronic hepatitis C virus (HCV) infection is a major etiology of hepatocellular carcinoma (HCC). For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. According to our previous report, the cumulated recurrence rate for small HCV-HCC was 72.4% at 5 year. PEG-interferon plus RBV treatment is the standard of care for chronic hepatitis C (CHC) in Taiwan. NHIRD data showed that PEG-IFN plus RBV treatment can reduce 12% of recurrence rate in 5 years (64% vs 52%) after curative resection of HCC. However, only selected patients are eligible and tolerable to IFN-based treatment after surgical resection and the sustained virological response varied.
Harvoni for genotype 1 HCV and sovaldi plus ribavirin for genotype 2 HCV can achieve high SVR and being recommended by AASLD and EASL. All-oral regimen, being more tolerable and effective for HCC patients after curative treatment than IFN-based treatment. Mixed HCV genotype infection accounts for 10% of CHC patients in Taiwan. Sovaldi-based treatment plus ribavirin should be as effective as Sovaldi plus rivavirin in the treatment of genotype 2 HCV, as well as mixed genotype 1 and 2 HCV infection. As genotype 1 and 2 are the leading HCV genotypes in Taiwan, It can simplify the regimen of anti-HCV treatment in Taiwan by using Harvoni plus ribavirin, not only for genotype 1 and 2 HCV but also for mixed genotype 1 and 2 HCV infection. Although an unexpected high recurrence rate in HCC patients under DAA treatment was reported once. However, one recent study showed a low risk of HCC recurrence after DAA treatment. Harvoni is an all-oral regimen, being more tolerable and effective for HCC patients after surgery than IFN-based treatment. The all oral regimen would be beneficial in eradicating HCV viral load and subsequently reduce the risk of recurrence after curative resection of HCV-HCC.
In this study, the investigators plan to enroll 130 HCV-HCC patients after confirming curative treatment for their HCC, either by surgery or RFA. For the cases fulfilling the inclusion/exclusion criteria, a 12 weeks Harvoni plus ribavirin treatment will be provided for all cases (single armed design). The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. The secondary objectives of the study are SVR 4/12/24 by DAA, regression of fibrosis, incidence of liver-related complications (EV bleeding, ascites) after DAA treatment, and overall survival for 5 years.
A hospital-based cohorts of HCV-related HCC undergoing surgical resection or RFA from Taipei Veterans General Hospital and Investigated Sites will be recruited as historical controls. The historical controls include HCV-HCC undergoing curative treatment without Peg-interferon plus ribavirin treatment (cohort 1) or with Peg-interferon plus ribavirin treatment (cohort 2) after curative treatment (surgical resection or RFA) for HCC.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Ledipasvir 90mg/Sofosbuvir 400 mg, Ribavirin
- Keywords
- Chronic hepatitis C, Hepatocellular Carcinoma, Direct-acting antiviral (DAA), Recurrence
- Medical subject headings
- Carcinoma, Hepatocellular, Hepatitis C, Chronic, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ledipasvir 90mg/Sofosbuvir 400 mgDrug
Also called DAA
A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.
RibavirinDrug
Also called rebetol
A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.
| Study group | Role | What they receive |
|---|---|---|
| DAA treatment arm | Other | Active DAA treatment ('Ledipasvir 90mg/Sofosbuvir 400 mg plus Ribavirin' ) for HCV-HCC patients after curative resection or ablation. Receives: Drug: Ledipasvir 90mg/Sofosbuvir 400 mg; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.
The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.
Measured: up to 5 years
Secondary outcomes (4)
SVR 4/12/24 by DAA
SVR: sustained virological response. DAA: direct antiviral agent. SVR 4/12/24 means undetectable HCV viral load 4/12/24 weeks after completing DAA treatment.
Measured: up to 5 years
Regression of fibrosis
Regression of fibrosis
Measured: up to 5 years
Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment
Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment
Measured: up to 5 years
Overall survival
Overall survival
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionJun 2022 (estimated)
- Study completionDec 2022 (estimated)
Why it stopped: The supplies of study drug were halted by Gilead Sciences Ltd.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Collaborators
- Kaohsiung Medical University Chung-Ho Memorial Hospital, China Medical University Hospital, Chi Mei Medical Hospital, Chiayi Christian Hospital, National Taiwan University Hospital, Chang Gung Memorial Hospital, Tri-Service General Hospital (TSGH), National Cheng-Kung University Hospital
- Responsible party
- Principal investigator, vghtpe user, Taipei Veterans General Hospital, Taiwan
- Investigators
- Yi-Hsiang Huang, MD, PhD, Principal investigator, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02959359
- Sponsor's protocol ID
- GILEAD IN-US-337-4109
- Status last verified
- Aug 2017
- First submitted
- 30 Oct 2016
- Last updated
- 7 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of DAA in Reducing the Risk of Recurrence After Curative Treatment of HCC in Patients With Chronic Hepatitis C and Early Stage HCC
- ClinicalTrials.gov ID
- NCT02959359
- Acronym / sponsor ID
- GILEAD IN-US-337-4109
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Chronic hepatitis C, Hepatocellular Carcinoma, Direct-acting antiviral (DAA), Recurrence
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The supplies of study drug were halted by Gilead Sciences Ltd.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Collaborators
- Kaohsiung Medical University Chung-Ho Memorial Hospital, China Medical University Hospital, Chi Mei Medical Hospital, Chiayi Christian Hospital, National Taiwan University Hospital, Chang Gung Memorial Hospital, Tri-Service General Hospital (TSGH), National Cheng-Kung University Hospital
- Study start
- Nov 2016
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 9 Nov 2016 (estimated)
- 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.
For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. Only selected patients are eligible and tolerable to IFN-based treatment after surgical resection and the sustained virological response varied.
Harvoni for genotype 1 HCV and sovaldi plus ribavirin for genotype 2 HCV can achieve high SVR and being recommended by AASLD and EASL. Mixed HCV genotype infection accounts for 10% of CHC patients in Taiwan. Sovaldi-based treatment plus ribavirin should be as effective as Sovaldi plus rivavirin in the treatment of genotype 2 HCV, as well as mixed genotype 1 and 2 HCV infection. As genotype 1 and 2 are the leading HCV genotypes in Taiwan, It can simplify the regimen of anti-HCV treatment in Taiwan by using Harvoni plus ribavirin, not only for genotype 1 and 2 HCV but also for mixed genotype 1 and 2 HCV infection. Although an unexpected high recurrence rate in HCC patients under DAA treatment was reported once. However, one recent study showed a low risk of HCC recurrence after DAA treatment. In this study, the investigators plan to enroll 130 HCV-HCC patients after confirming curative treatment for their HCC, either by surgery or RFA. For the cases fulfilling the inclusion/exclusion criteria, a 12 weeks Harvoni plus ribavirin treatment will be provided for all cases (single armed design). The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. A hospital-based cohorts of HCV-related HCC undergoing surgical resection or RFA from Taipei Veterans General Hospital and Investigated Sites will be recruited as historical controls.
Detailed description
Chronic hepatitis C virus (HCV) infection is a major etiology of hepatocellular carcinoma (HCC). For early stage of HCC, surgical resection or radiofrequency ablation (RFA) is the mainstay curative treatments. However, recurrence is still a major issue after the surgery or RFA. According to our previous report, the cumulated recurrence rate for small HCV-HCC was 72.4% at 5 year. PEG-interferon plus RBV treatment is the standard of care for chronic hepatitis C (CHC) in Taiwan. NHIRD data showed that PEG-IFN plus RBV treatment can reduce 12% of recurrence rate in 5 years (64% vs 52%) after curative resection of HCC. However, only selected patients are eligible and tolerable to IFN-based treatment after surgical resection and the sustained virological response varied.
Harvoni for genotype 1 HCV and sovaldi plus ribavirin for genotype 2 HCV can achieve high SVR and being recommended by AASLD and EASL. All-oral regimen, being more tolerable and effective for HCC patients after curative treatment than IFN-based treatment. Mixed HCV genotype infection accounts for 10% of CHC patients in Taiwan. Sovaldi-based treatment plus ribavirin should be as effective as Sovaldi plus rivavirin in the treatment of genotype 2 HCV, as well as mixed genotype 1 and 2 HCV infection. As genotype 1 and 2 are the leading HCV genotypes in Taiwan, It can simplify the regimen of anti-HCV treatment in Taiwan by using Harvoni plus ribavirin, not only for genotype 1 and 2 HCV but also for mixed genotype 1 and 2 HCV infection. Although an unexpected high recurrence rate in HCC patients under DAA treatment was reported once. However, one recent study showed a low risk of HCC recurrence after DAA treatment. Harvoni is an all-oral regimen, being more tolerable and effective for HCC patients after surgery than IFN-based treatment. The all oral regimen would be beneficial in eradicating HCV viral load and subsequently reduce the risk of recurrence after curative resection of HCV-HCC.
In this study, the investigators plan to enroll 130 HCV-HCC patients after confirming curative treatment for their HCC, either by surgery or RFA. For the cases fulfilling the inclusion/exclusion criteria, a 12 weeks Harvoni plus ribavirin treatment will be provided for all cases (single armed design). The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. The secondary objectives of the study are SVR 4/12/24 by DAA, regression of fibrosis, incidence of liver-related complications (EV bleeding, ascites) after DAA treatment, and overall survival for 5 years.
A hospital-based cohorts of HCV-related HCC undergoing surgical resection or RFA from Taipei Veterans General Hospital and Investigated Sites will be recruited as historical controls. The historical controls include HCV-HCC undergoing curative treatment without Peg-interferon plus ribavirin treatment (cohort 1) or with Peg-interferon plus ribavirin treatment (cohort 2) after curative treatment (surgical resection or RFA) for HCC.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DAA treatment arm | Other | Drug: Ledipasvir 90mg/Sofosbuvir 400 mg, Drug: RibavirinActive DAA treatment ('Ledipasvir 90mg/Sofosbuvir 400 mg plus Ribavirin' ) for HCV-HCC patients after curative resection or ablation. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Anti-HCV positive and HBsAg-negative
- HCV genotype 1 or 2 infection, mixed infection GT 1 \& 2 is allowed
- HCV RNA ≥ 10,000 IU/ml at the time of screening
- Age > 20 y/o
- BCLC stage 0 or A HCC confirmed by pathology and receiving the first time of curative treatment
Key exclusion criteria (5 listed)
- HBV, or HIV coinfection
- Co-existing other malignancy
- Intolerance to ribavirin
- Marked decompensated liver cirrhosis (CTP score>7)
- Uremia or renal impaired patients (eGFR<30)
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 |
|---|---|---|
| Ledipasvir 90mg/Sofosbuvir 400 mgAlso: DAAA 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment. | Drug | DAA treatment arm |
| RibavirinAlso: rebetolA 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment. | Drug | DAA treatment arm |
Primary outcome
The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.
Time frame: up to 5 years
The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.
4 secondary outcomes
SVR 4/12/24 by DAA
Time frame: up to 5 years
Regression of fibrosis
Time frame: up to 5 years
Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment
Time frame: up to 5 years
Overall survival
Time frame: up to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2017.
- Individual participant dataSharing planned: Undecided
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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.
Yi-Hsiang Huang, MD, PhD principal investigator
Taipei Veterans General Hospital, Taiwan
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ledipasvir 90mg/Sofosbuvir 400 mg and Ribavirin in people with Hepatocellular Carcinoma, run by Taipei Veterans General Hospital, 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 8 inclusion and 5 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: withdrawn, as of the sponsor's last update on 7 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
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 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. (time frame: up to 5 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 7 Aug 2017.