NCT04680598

Brief 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). 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
800

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Dec 2020

Typical duration for all trials

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 17, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

December 23, 2020

Completed
2 days until next milestone

Study Start

First participant enrolled

December 25, 2020

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed
Last Updated

August 2, 2023

Status Verified

August 1, 2023

Enrollment Period

3 years

First QC Date

December 17, 2020

Last Update Submit

August 1, 2023

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

  • 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)

    2 months

Secondary Outcomes (4)

  • HBV-associated hepatitis

    2 months

  • PD-1 inhibitor disruption due to hepatitis

    2 months

  • overall survival

    12 months

  • adverse event

    30 Days after ICI

Study Arms (2)

high HBV-DNA group

patients with HBV-DNA \>500 IU/ml

Drug: ICIDrug: Antiviral Prophylaxis

low HBV-DNA group

patients with HBV-DNA≤500 IU/ml

Drug: ICIDrug: Antiviral Prophylaxis

Interventions

ICIDRUG

Patients received ICI, including PD-1 inhibitor (pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab) or PD-L1 inhibitor (atezolizumab)

high HBV-DNA grouplow HBV-DNA group
Antiviral ProphylaxisDRUG

Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir

high HBV-DNA grouplow HBV-DNA group

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
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.

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Cancer Center Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

Guangzhou Twelfth People 's Hospital

Guangzhou, Guangdong, 510620, China

RECRUITING

Kaiping Central Hospital

Kaiping, Guangdong, 529300, China

RECRUITING

ZhongShan People 's Hospital

Zhongshan, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Proffessor

Study Record Dates

First Submitted

December 17, 2020

First Posted

December 23, 2020

Study Start

December 25, 2020

Primary Completion

December 31, 2023

Study Completion

December 31, 2023

Last Updated

August 2, 2023

Record last verified: 2023-08

Locations

CN(4)