Tenofovir Antiviral Therapy Following Transarterial Chemoembolization for HBV Related Hepatocellular Carcinoma

September 3, 2014 updated by: Chun-Ying Wu, Taichung Veterans General Hospital

Tenofovir Disoproxil Fumarate Improves Outcomes Following Palliative Transarterial Chemoembolization for Hepatitis B Virus Related Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common solid cancers worldwide, and chronic hepatitis B virus (HBV) infection is the most common etiology of HCC in Asia. Transarterial chemoembolization (TACE) is the standard treatment for patients with unresectable HCC in the BCLC intermediate stage, but the HCC recurrence rates and long-term mortality rates are quite high. These intermediate-staged HCC patients usually need repeated TACE due to tumor recurrence, and they may die of HCC progression or liver decompensation after repeated TACE. Improved liver function and decreased liver disease progression due to oral antiviral therapy have been proven to be effective for chronic hepatitis B, and oral antiviral therapy may keep better liver reserve and provide better chance for HCC patients received TACE. In addition, chronic HBV infection is one of the most important factors for HCC development, and antiviral therapy can improve the outcomes after curative treatment. However, the evidence of improving outcomes of HCC patients underwent TACE by oral antiviral therapy is lacking. Moreover, Tenofovir Disoproxil Fumarate (TDF) is one of the most potent oral antiviral agents, and its safety and very low long-term viral resistance rate have been also reported. There is no study to evaluate the impacts of TDF for HBV-related HCC patients underwent TACE. Until now, routine antiviral therapy for HBV-related HCC patients underwent TACE has still not been recommended by current guidelines. The hypothesis of this study is that a potent oral antiviral therapy for patients with HBV-related HCC patients receiving TACE improve patients' outcomes

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is randomized double-blind placebo-controlled trial that will be conducted in referral teaching hospitals in Taiwan. This trial will recruit 320 patients fulfilling all of the following criteria: patients more than 20 years old, HCCs diagnosed by AASLD image criteria or pathology, medium-sized HCCs in BCLC intermediate stage and not more than 5 cm in maximum diameter and not more than 5 tumors that TACE is indicated, chronic HBV carrier (HBsAg+) with detectable HBV DNA in blood, ECOG performance status (PST) 0-2, Child-Pugh score ≦7, serum bilirubin < 2 mg/dL and prothrombin time (PT) prolongation < 3 seconds, and willingness to adhere to treatment and follow-up plans. Patients are ineligible if they have any of the following exclusion criteria: any vascular invasion by tumors, extra-hepatic metastasis, concurrent any other malignancy, concomitant immunosuppressive therapy, previous any HCC treatment, previous or current any antiviral therapy for HBV, concomitant other therapies for HCC except TACE, liver cirrhosis with severe gastroesophageal varices (EVF3 or with red color sign), poorly-controlled ascites or hepatic encephalopathy, contraindication for invasive procedures such as recent gastrointestinal bleeding or cerebral hemorrhage, contraindication to TACE such as allergy to contrast, pregnancy, sepsis, etc., chronic renal failure with eGFR < 60, concurrent any other chronic viral hepatitis with HCV, HDV, or HIV). The Primary endpoints of this study will be 1-, 3-year overall survival, and the secondary endpoints of this study will be time to tumor progression and time to liver decompensation.

Study Type

Interventional

Enrollment (Anticipated)

320

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Chia-Yi, Taiwan, 539
        • Chia-Yi Christine Hospital
      • Kaohsiung, Taiwan, 824
        • E-Da Hospital
      • Taichung, Taiwan, 407
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 104
        • Mackay Memorial Hosp

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. more than 20 years old
  2. HCCs diagnosed by AASLD image criteria or pathology
  3. Intermediate-stage HCCs that TACE is indicated
  4. chronic HBV carrier with detectable HBV DNA in blood
  5. ECOG performance status (PST) 0-2
  6. Child-Pugh score ≦7
  7. serum bilirubin < 2 mg/dL
  8. prothrombin time prolongation < 3 seconds
  9. willingness to adhere to treatment and follow-up plans -

Exclusion Criteria:

  1. any vascular invasion by tumors
  2. extra-hepatic metastasis
  3. concurrent any other malignancy
  4. concomitant immunosuppressive therapy
  5. HCC recurrence within 2 years of previous curative treatment
  6. antiviral therapy for chronic hepatitis B within 6 months before HCC diagnosis
  7. concomitant other therapies for HCC except TACE
  8. liver cirrhosis with severe gastroesophageal varices (EVF3 or with red color sign), poorly-controlled ascites or hepatic encephalopathy
  9. contraindication for invasive procedures such as recent gastrointestinal bleeding or cerebral hemorrhage
  10. contraindication to TACE such as allergy to contrast, pregnancy, sepsis, etc.
  11. chronic renal failure with eGFR < 60
  12. concurrent any other chronic viral hepatitis with HCV, HDV, or HIV) -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Tenofovir treatment
Start to administer Tenofovir treatment 300mg PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years.
Drug: Tenofovir
Administer Tenofovir to HCC patients who are indicated for TACE after randomization
Other Names:
  • Viread
PLACEBO_COMPARATOR: Placebo
Start to administer placebo 1 Tab PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years.
Drug: Placebo
Administer Placebo to HCC patients who are indicated for TACE after randomization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
overall survival
Time Frame: up to 3-year
up to 3-year

Secondary Outcome Measures

Outcome Measure
Time Frame
time to tumor progression
Time Frame: 1- and 3-year
1- and 3-year
time to liver decompensation
Time Frame: 1- and 3-year
1- and 3-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taichung Veterans General Hospital

Collaborators

Gilead Sciences
Taipei Institute of Pathology

Investigators

  • Principal Investigator: Chun-Ying Wu, MD, PhD, MPH, Taichung Veterans General Hospital
  • Study Chair: Jaw-Town Lin, MD, PhD, Fu Jen Catholic University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (ANTICIPATED)

February 1, 2018

Study Completion (ANTICIPATED)

February 1, 2018

Study Registration Dates

First Submitted

January 30, 2013

First Submitted That Met QC Criteria

June 6, 2013

First Posted (ESTIMATE)

June 7, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

September 4, 2014

Last Update Submitted That Met QC Criteria

September 3, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CF12045
  • JIRB11-036-A (OTHER: JIRB, Taiwan)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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