DAA in the Risk of Recurrence After Curative Treatment of HCC

NCT ID: NCT02959359

Last Updated: 2017-08-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2022-12-31

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

DAA treatment arm

Active DAA treatment ('Ledipasvir 90mg/Sofosbuvir 400 mg plus Ribavirin' ) for HCV-HCC patients after curative resection or ablation.

Group Type: OTHER

Ledipasvir 90mg/Sofosbuvir 400 mg

Intervention Type: DRUG

A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.

Ribavirin

Intervention Type: DRUG

A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.

Interventions

Ledipasvir 90mg/Sofosbuvir 400 mg

A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.

Intervention Type: DRUG

Ribavirin

A 12 week Harvoni (Ledipasvir 90mg/Sofosbuvir 400 mg ) plus ribavirin will be provided after confirmation of curative treatment.

Intervention Type: DRUG

Other Intervention Names

DAA; rebetol

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)

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaohsiung Medical University Chung-Ho Memorial Hospital

OTHER

Sponsor Role: collaborator

China Medical University Hospital

OTHER

Sponsor Role: collaborator

Chi Mei Medical Hospital

OTHER

Sponsor Role: collaborator

Chiayi Christian Hospital

OTHER

Sponsor Role: collaborator

National Taiwan University Hospital

OTHER

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: collaborator

Tri-Service General Hospital

OTHER

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: lead

Responsible Party

vghtpe user

Professor Yi-Hsiang Huang

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yi-Hsiang Huang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Taipei Veterans General Hospital, Taiwan

Other Identifiers

GILEAD IN-US-337-4109

Identifier Type: -

Identifier Source: org_study_id