Clinical trial NCT02959359: DAA in the Risk of Recurrence After Curative Treatment of HCC
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Hepatocellular Carcinoma
Keywords: Chronic hepatitis C
Hepatocellular Carcinoma
Direct-acting antiviral (DAA)
Recurrence
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
Collaborators: name: Kaohsiung Medical University Chung-Ho Memorial Hospital
name: China Medical University Hospital
name: Chi Mei Medical Hospital
name: Chiayi Christian Hospital
name: National Taiwan University Hospital
name: Chang Gung Memorial Hospital
name: Tri-Service General Hospital
name: National Cheng-Kung University Hospital
First posted: 2016-11-09
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: The primary objective of the study is annual recurrence-free survival after curative resection of HCV-HCC for up to 5 years.
timeFrame: up to 5 years
Secondary outcomes:
measure: SVR 4/12/24 by DAA
timeFrame: up to 5 years
measure: Regression of fibrosis
timeFrame: up to 5 years
measure: Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment
timeFrame: up to 5 years
measure: Overall survival
timeFrame: up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Yi-Hsiang Huang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: