DAA in the Risk of Recurrence After Curative Treatment of HCC
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT02959359
- Lead Sponsor
- Taipei Veterans General Hospital, Taiwan
- Brief 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. 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description DAA treatment arm Ledipasvir 90mg/Sofosbuvir 400 mg Active DAA treatment ('Ledipasvir 90mg/Sofosbuvir 400 mg plus Ribavirin' ) for HCV-HCC patients after curative resection or ablation. DAA treatment arm Ribavirin Active DAA treatment ('Ledipasvir 90mg/Sofosbuvir 400 mg plus Ribavirin' ) for HCV-HCC patients after curative resection or ablation.
- Primary Outcome Measures
Name Time Method The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years. 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.
- Secondary Outcome Measures
Name Time Method Overall survival up to 5 years Overall survival
Regression of fibrosis up to 5 years Regression of fibrosis
Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment up to 5 years Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment
SVR 4/12/24 by DAA up to 5 years 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.