Chronic Hepatitis BPhase 3NCT01872988
Tenofovir Antiviral Therapy Following Transarterial Chemoembolization for HBV Related Hepatocellular Carcinoma
A Phase 3 study testing Tenofovir in people with Chronic Hepatitis B and Hepatocellular Carcinoma, run by Taichung Veterans General Hospital at 4 sites in Taiwan.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Chronic Hepatitis B, Hepatocellular Carcinoma
- What is being tested?
- Tenofovir
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 320 participants
- Where
- 4 sitesTaiwan
- Study dates
- Sep 2012to Feb 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- more than 20 years old
- HCCs diagnosed by AASLD image criteria or pathology
- Intermediate-stage HCCs that TACE is indicated
- chronic HBV carrier with detectable HBV DNA in blood
- ECOG performance status (PST) 0-2
- Child-Pugh score ≦7
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- serum bilirubin < 2 mg/dL
- prothrombin time prolongation < 3 seconds
- willingness to adhere to treatment and follow-up plans -
Who cannot join
- any vascular invasion by tumors
- extra-hepatic metastasis
- concurrent any other malignancy
- concomitant immunosuppressive therapy
- HCC recurrence within 2 years of previous curative treatment
- antiviral therapy for chronic hepatitis B within 6 months before HCC diagnosis
Show all 12Show fewer
- 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) -
Trial locations and contacts
4 sites in 1 country.
Taiwan4 sites
Chia-Yi Christine Hospital
Chiayi City, 539
E-Da Hospital
Kaohsiung City, 824
Taichung Veterans General Hospital
Taichung, 407
Mackay Memorial Hosp
Taipei, 104
About this study
Official title: 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
Read the 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.
- Conditions
- Chronic Hepatitis B, Hepatocellular Carcinoma
- Being tested
- Tenofovir, Placebo
- Keywords
- antiviral therapy, intermediate stage, hepatitis B virus
- Medical subject headings
- Hepatitis B, Chronic, Carcinoma, Hepatocellular, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TenofovirDrug
Also called Viread
Administer Tenofovir to HCC patients who are indicated for TACE after randomization
PlaceboDrug
Administer Placebo to HCC patients who are indicated for TACE after randomization
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir treatment | Active comparator | Start to administer Tenofovir treatment 300mg PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years. Receives: Drug: Tenofovir |
| Placebo | Placebo comparator | Start to administer placebo 1 Tab PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival
Measured: up to 3-year
Secondary outcomes (2)
time to tumor progression
Measured: 1- and 3-year
time to liver decompensation
Measured: 1- and 3-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2013 (estimated)
- Study startSep 2012
- Primary completionFeb 2018 (estimated)
- Study completionFeb 2018 (estimated)
Why it stopped: Difficult in patient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Taichung Veterans General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taichung Veterans General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences, Taipei Institute of Pathology
- Responsible party
- Principal investigator, Chun-Ying Wu, Taichung Veterans General Hospital
- Investigators
- Chun-Ying Wu, MD, PhD, MPH, Principal investigator, Taichung Veterans General HospitalJaw-Town Lin, MD, PhD, Study chair, Fu Jen Catholic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01872988
- Sponsor's protocol ID
- CF12045
- Other IDs
- JIRB11-036-A
- Status last verified
- Sep 2014
- First submitted
- 30 Jan 2013
- Last updated
- 4 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X.
PubMed 12049862Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.
PubMed 11981766
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenofovir Disoproxil Fumarate Improves Outcomes Following Palliative Transarterial Chemoembolization for Hepatitis B Virus Related Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT01872988
- Acronym / sponsor ID
- CF12045
- Conditions
- Chronic Hepatitis B, Hepatocellular Carcinoma
- Keywords
- antiviral therapy, intermediate stage, hepatitis B virus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficult in patient enrollment
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Taichung Veterans General HospitalUniversity, hospital or other
- Collaborators
- Gilead Sciences, Taipei Institute of Pathology
- Study start
- Sep 2012
- Primary completion
- Feb 2018 (estimated)
- Study completion
- Feb 2018 (estimated)
- First posted
- 7 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tenofovir treatment | Active comparator | Drug: TenofovirStart to administer Tenofovir treatment 300mg PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years. |
| Placebo | Placebo comparator | Drug: PlaceboStart to administer placebo 1 Tab PO QD within 2 weeks after the 1st TACE. Maximum duration of tenofovir treatment: 3 years. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- more than 20 years old
- HCCs diagnosed by AASLD image criteria or pathology
- Intermediate-stage HCCs that TACE is indicated
- chronic HBV carrier with detectable HBV DNA in blood
- ECOG performance status (PST) 0-2
Key exclusion criteria (12 listed)
- any vascular invasion by tumors
- extra-hepatic metastasis
- concurrent any other malignancy
- concomitant immunosuppressive therapy
- HCC recurrence within 2 years of previous curative treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TenofovirAlso: VireadAdminister Tenofovir to HCC patients who are indicated for TACE after randomization | Drug | Tenofovir treatment |
| PlaceboAdminister Placebo to HCC patients who are indicated for TACE after randomization | Drug | Placebo |
Primary outcome
overall survival
Time frame: up to 3-year
2 secondary outcomes
time to tumor progression
Time frame: 1- and 3-year
time to liver decompensation
Time frame: 1- and 3-year
Results and safety
The study was stopped early (reason given: Difficult in patient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2014.
- Background: PubMed 12049862Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9. doi: 10.1016/S0140-6736(02)08649-X.
- Background: PubMed 11981766Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71. doi: 10.1053/jhep.2002.33156.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chun-Ying Wu, MD, PhD, MPH principal investigator
Taichung Veterans General Hospital
Jaw-Town Lin, MD, PhD study chair
Fu Jen Catholic University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tenofovir in people with Chronic Hepatitis B and Hepatocellular Carcinoma, run by Taichung Veterans General Hospital at 4 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficult in patient enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (time frame: up to 3-year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01872988, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2014.