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Comparison of HBV Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing PD-1 Inhibitor and Concurrent Antiviral Prophylaxis: a Prospective Observational Study

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ClinicalTrials.gov Identifier: NCT04680598
Recruitment Status : Recruiting
First Posted : December 23, 2020
Last Update Posted : January 13, 2021
Sponsor:
Collaborators:
Kaiping Central Hospital
Guangzhou No.12 People's Hospital
Information provided by (Responsible Party):
Shi Ming, Sun Yat-sen University

Brief Summary:
rogrammed cell death protein-1 (PD-1) inhibitor is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of PD-1 inhibitor 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 PD-1 inhibitor.

Condition or disease Intervention/treatment
Hepatocellular Carcinoma Drug: PD-1 inhibitor Drug: Antiviral Prophylaxis

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Comparison of Hepatitis B Virus Reactivation Between Patients With High HBV-DNA and Low HBV-DNA Loads Undergoing Programmed Cell Death Protein-1 Inhibitor and Concurrent Antiviral Prophylaxis: a Prospective Observational Study
Actual Study Start Date : December 25, 2020
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2022


Group/Cohort Intervention/treatment
high HBV-DNA group
patients with HBV-DNA >500 IU/ml
Drug: PD-1 inhibitor
Patients received PD-1 inhibtor, such as pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab

Drug: Antiviral Prophylaxis
Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir

low HBV-DNA group
patients with HBV-DNA≤500 IU/ml
Drug: PD-1 inhibitor
Patients received PD-1 inhibtor, such as pembrolizumab, toripalimab, nivolumab, sintilimab, camrelizumab

Drug: Antiviral Prophylaxis
Patient received concurrent antiviral prophylaxis, such as tenofovir, entecavir




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. HBV-associated hepatitis [ Time Frame: 2 months ]
    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

  2. PD-1 inhibitor disruption due to hepatitis [ Time Frame: 2 months ]
    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.

  3. overall survival [ Time Frame: 12 months ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-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 PD-1 inhibitor 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 PD-1 inhibitor therapy. Antiviral prophylaxis was defined as anti-HBV treatment administered before and during PD-1 inhibitor therapy. Antiviral treatment was continued even though PD-1 inhibitor therapy was terminated.
Criteria

Inclusion Criteria:

  • 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 PD-1 inhibitor 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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04680598


Locations
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China, Guangdong
Cancer Center Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Ming Shi, MD    8620-87343115    shiming@mail.sysu.edu.cn   
Guangzhou Twelfth People 's Hospital Recruiting
Guangzhou, Guangdong, China, 510620
Contact: Yuanmin Zhou, MD    15521278919    13430288977@139.com   
Principal Investigator: Jinghua Chen, MD         
Kaiping Central Hospital Recruiting
Kaiping, Guangdong, China, 529300
Contact: Shijie Zhang, MD    13717287622    Shijie_9262511@163.com   
Sponsors and Collaborators
Sun Yat-sen University
Kaiping Central Hospital
Guangzhou No.12 People's Hospital
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Responsible Party: Shi Ming, Proffessor, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04680598    
Other Study ID Numbers: SH-2
First Posted: December 23, 2020    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antiviral Agents
Anti-Infective Agents