Hepatocellular CarcinomaNCT04680598
Comparison of HBV Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing ICI and Concurrent Antiviral Prophylaxis: a Prospective Observational Study
An observational study of Hepatocellular Carcinoma, run by Sun Yat-sen University at 4 sites in China.
Trial summary
Immune checkpoint inhibitor (ICI), including programmed cell death protein-1 (PD-1) inhibitor or programmed cell death-Ligand 1 (PD-L1) inhibitor , is recommended to treat advanced hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- ICI and Antiviral Prophylaxis
- How many people
- 800 participants
- Where
- 4 sitesChina
- Study dates
- 25 Dec 2020to 31 Dec 2023
- Phase
- Observational
- 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 18 to 75 years
- All sexes
- Adult, Older adult
Study population: Eligible patients were divided into low HBV-DNA group (low group, ≤500 IU/ml) and high HBV-DNA group (high group, >500 IU/ml) according to baseline HBV-DNA level. Baseline HBV-DNA was the HBV-DNA level within 2 weeks prior to initial ICI therapy. For patients who had prior experience with antiviral therapy, the antiviral therapy would be continued. For patients who did not have prior experience with antiviral therapy, antiviral therapy would be administered after patients was confirmed with positive HBsAg or positive HBV-DNA level. Prior use of antiviral therapy was defined that patients have taken antiviral therapy for a period of time before they received ICI therapy. Antiviral prophylaxis was defined as anti-HBV treatment administered before and during ICI therapy. Antiviral treatment was continued even though ICI therapy was terminated.
Who may be able to join
- The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
- Seropositive for hepatitis B surface antigen (HBsAg)
- Received concurrent antiviral prophylaxis and at least one cycle of ICI treatment. Prior use of antiviral therapy was allowed
- Adherence to antiviral therapy
- A life expectancy of 3 months or more
- An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
Who cannot join
- other positive viral markers, including IgM antibodies to hepatitis A virus, the hepatitis C virus viral load, IgG antibodies to hepatitis D virus, IgM antibodies to hepatitis E virus
- Antibodies to human immunodeficiency virus,
- A lack of HBV DNA and liver function testing before the first immunotherapy and during the follow-up period.
Trial locations and contacts
4 sites in 1 country.
China4 sites, 4 recruiting
- Recruiting
Cancer Center Sun Yat-sen University
Guangzhou, Guangdong, 510060
Ming Shi, MD, 8620-87343115, shiming@mail.sysu.edu.cn
- Recruiting
Guangzhou Twelfth People 's Hospital
Guangzhou, Guangdong, 510620
Yuanmin Zhou, MD, 15521278919, 13430288977@139.com
Jinghua Chen, MD
- Recruiting
Kaiping Central Hospital
Kaiping, Guangdong, 529300
Shijie Zhang, MD, 13717287622, Shijie_9262511@163.com
- Recruiting
ZhongShan People 's Hospital
Zhongshan
Peng Peng, 13501509619, 1547463629@qq.com
About this study
Official title: Comparison of Hepatitis B Virus Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing Immune Checkpoint Inhibitor and Concurrent Antiviral Prophylaxis: a Prospective Observational Study
Immune checkpoint inhibitor (ICI), including programmed cell death protein-1 (PD-1) inhibitor or programmed cell death-Ligand 1 (PD-L1) inhibitor , is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of ICI in patients with a high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and ICI.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- ICI, Antiviral Prophylaxis
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICIDrug
Patients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab)
Antiviral ProphylaxisDrug
Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir
| Study group | Role | What they receive |
|---|---|---|
| high HBV-DNA group | patients with HBV-DNA >500 IU/ml Receives: Drug: ICI; Drug: Antiviral Prophylaxis | |
| low HBV-DNA group | patients with HBV-DNA≤500 IU/ml Receives: Drug: ICI; Drug: Antiviral Prophylaxis |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBV Reactivation rate
HBV Reactivation rate was defined as one of the following according to the American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidelines: (i) a ≥2 log (100-fold) increase in HBV DNA compared to the baseline level, (ii) HBV DNA ≥3 log (1,000) IU/mL in a patient with previously undetectable level (since HBV DNA levels fluctuate)
Measured: 2 months
Secondary outcomes (4)
HBV-associated hepatitis
HBV-associated hepatitis was defined as HBV Reactivation plus an ALT increase to ≥3 times the baseline level and >100 U/L according to the AASLD 2018 Hepatitis B Guidance
Measured: 2 months
PD-1 inhibitor disruption due to hepatitis
PD-1 inhibitor disruption due to hepatitis was defined as either premature termination or a delay of at least 7 days between PD-1 inhibitor cycles because of hepatitis.
Measured: 2 months
overall survival
Measured: 12 months
adverse event
Measured: 30 Days after ICI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start25 Dec 2020
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Kaiping Central Hospital, Guangzhou No.12 People's Hospital, ZhongShan People 's Hospital
- Responsible party
- Principal investigator, Shi Ming, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04680598
- Sponsor's protocol ID
- SH003
- Status last verified
- Aug 2023
- First submitted
- 17 Dec 2020
- Last updated
- 2 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Hepatitis B Virus Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing Immune Checkpoint Inhibitor and Concurrent Antiviral Prophylaxis: a Prospective Observational Study
- ClinicalTrials.gov ID
- NCT04680598
- Acronym / sponsor ID
- SH003
- Conditions
- Hepatocellular Carcinoma
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Kaiping Central Hospital, Guangzhou No.12 People's Hospital, ZhongShan People 's Hospital
- Study start
- 25 Dec 2020 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 23 Dec 2020 (actual)
- 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.
Immune checkpoint inhibitor (ICI), including programmed cell death protein-1 (PD-1) inhibitor or programmed cell death-Ligand 1 (PD-L1) inhibitor , is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of ICI in patients with a high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and ICI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| high HBV-DNA group | – | Drug: ICI, Drug: Antiviral Prophylaxispatients with HBV-DNA >500 IU/ml |
| low HBV-DNA group | – | Drug: ICI, Drug: Antiviral Prophylaxispatients with HBV-DNA≤500 IU/ml |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Eligible patients were divided into low HBV-DNA group (low group, ≤500 IU/ml) and high HBV-DNA group (high group, >500 IU/ml) according to baseline HBV-DNA level. Baseline HBV-DNA was the HBV-DNA level within 2 weeks prior to initial ICI therapy. For patients who had prior experience with antiviral therapy, the antiviral therapy would be continued. For patients who did not have prior experience with antiviral therapy, antiviral therapy would be administered after patients was confirmed with positive HBsAg or positive HBV-DNA level. Prior use of antiviral therapy was defined that patients have taken antiviral therapy for a period of time before they received ICI therapy. Antiviral prophylaxis was defined as anti-HBV treatment administered before and during ICI therapy. Antiviral treatment was continued even though ICI therapy was terminated.
Key inclusion criteria (6 listed)
- The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
- Seropositive for hepatitis B surface antigen (HBsAg)
- Received concurrent antiviral prophylaxis and at least one cycle of ICI treatment. Prior use of antiviral therapy was allowed
- Adherence to antiviral therapy
- A life expectancy of 3 months or more
Key exclusion criteria (3 listed)
- other positive viral markers, including IgM antibodies to hepatitis A virus, the hepatitis C virus viral load, IgG antibodies to hepatitis D virus, IgM antibodies to hepatitis E virus
- Antibodies to human immunodeficiency virus,
- A lack of HBV DNA and liver function testing before the first immunotherapy and during the follow-up period.
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 |
|---|---|---|
| ICIPatients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab) | Drug | high HBV-DNA group, low HBV-DNA group |
| Antiviral ProphylaxisPatient received concurrent antiviral prophylaxis, such as tenofovir, entecavir | Drug | high HBV-DNA group, low HBV-DNA group |
Primary outcome
HBV Reactivation rate
Time frame: 2 months
HBV Reactivation rate was defined as one of the following according to the American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidelines: (i) a ≥2 log (100-fold) increase in HBV DNA compared to the baseline level, (ii) HBV DNA ≥3 log (1,000) IU/mL in a patient with previously undetectable level (since HBV DNA levels fluctuate)
4 secondary outcomes
HBV-associated hepatitis
Time frame: 2 months
PD-1 inhibitor disruption due to hepatitis
Time frame: 2 months
overall survival
Time frame: 12 months
adverse event
Time frame: 30 Days after ICI
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2023.
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma, run by Sun Yat-sen University at 4 sites in China.
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 6 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 2 Aug 2023. 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 China. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBV Reactivation rate (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Aug 2023.