DAA in the Risk of Recurrence After Curative Treatment of HCC

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02959359
• Other study ID #: GILEAD IN-US-337-4109
• Status: Withdrawn
• Phase: Phase 4
• First received: October 30, 2016
• Last updated: August 4, 2017
• Start date: November 2016
• Est. completion date: December 2022

Study information

• Verified date: August 2017
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Recurrence

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (9)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan	Chang Gung Memorial Hospital, Chi Mei Medical Hospital, Chiayi Christian Hospital, China Medical University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, National Cheng-Kung University Hospital, National Taiwan University Hospital, Tri-Service General Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 5 years
Secondary	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.	up to 5 years
Secondary	Regression of fibrosis	Regression of fibrosis	up to 5 years
Secondary	Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment	Incidence of liver-related complications (EV bleeding, ascites) after DAA treatment	up to 5 years
Secondary	Overall survival	Overall survival	up to 5 years