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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
320

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
overall survival
Time Frame: up to 3-year
up to 3-year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Taichung Veterans General Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Gilead Sciences
Taipei Institute of Pathology

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2012

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2018

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 7, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 4, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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