Post-Radical Treatment Antiviral Strategies in HBV-Related Liver Cancer: Impact on Tumor Prognosis

Official title

The Impact of Different Antiviral Strategies on Tumor Prognosis in Patients With HBV-related Liver Cancer After Radical Treatment: A Prospective, Open-label, Non-randomized Clinical Study

Overview

The goal of this clinical trial is to learn if peginterferon alfa-2b can reduce the recurrence of HBV-related liver cancer in patients who have undergone radical treatment. The study will also explore the potential benefits of peginterferon alfa-2b in achieving clinical cure and its impact on reducing liver cancer recurrence. The trial is designed as a single-center, non-randomized, open-label study. Participants will be HBV-related liver cancer patients who have received radical treatment. The study will compare two groups: one receiving nucleos(t)ide analogues (NAs) alone and the other receiving NAs combined with peginterferon alfa-2b. The main question it aims to answer is: Can peginterferon alfa-2b lower the 3-year recurrence rate in HBV-related liver cancer patients after radical treatment? Participants will undergo regular follow-ups, including imaging studies and blood tests, to monitor for cancer recurrence and assess the safety of the treatment.

Detailed description

1. Study Background The 3-year recurrence rate of HBV-related liver cancer after radical surgery is as high as 40% to 70%. This study aims to explore whether the addition of peginterferon alfa-2b (Peg-IFNα-2b) to nucleoside (acid) analogues (NAs) can reduce the risk of recurrence through immune modulation. 2. Key Mechanism Hypotheses

Peg-IFNα-2b may reduce the reactivation of micrometastases through: * Enhancing HBV-specific T-cell responses * Lowering serum HBsAg levels * Inhibiting immune suppression in the tumor microenvironment 3. Detection Methods

* Imaging Monitoring: Abdominal MRI (using LI-RADS v2018 criteria) every 12 weeks ± 7 days. * Laboratory Tests: * HBV DNA: COBAS® TaqMan HBV Test (LLOQ = 10 IU/mL) * Quantitative HBsAg: Architect HBsAg QT assay * PBMC Immune Profile: Flow cytometry (proportion of CD8+/PD-1+ T cells) * Tissue Biomarkers: Postoperative tumor tissue PD-L1 immunohistochemistry (22C3 antibody) and T-cell infiltration score. 4. Statistical Design

* Sample size: 332 cases (power 80%, α = 0.05, expected HR = 0.6) * Primary endpoint analysis: 3-year cumulative recurrence rate (Kaplan-Meier method + Log-rank test) * Covariate adjustment: Cox model includes age, BCLC stage, and baseline HBsAg level.

Interventions

• Drug Intervention for Group 1
  Participants will receive standard NAs therapy, which may include entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or tenofovir amibufenamide (TMF). NAs are antiviral medications used to suppress HBV replication and manage chronic hepatitis B infection.
• Drug Intervention for Group 2
  Participants will receive Peg-IFNα-2b in addition to NAs therapy. Peg-IFNα-2b is an antiviral medication that works by boosting the immune system and has additional antiviral, antifibrotic, and anti-tumor effects. It is used to treat chronic hepatitis B and may help reduce the recurrence of liver cancer.

Primary outcome measures

• 3-Year Cumulative Recurrence Rate via MRI (LI-RADS) [Time frame: 3 years post-radical treatment.]

Secondary outcome measures (6)

• 2-Year HBsAg Seroclearance Rate [Time frame: 2 years post-treatment initiation.]
• 2-Year HBV DNA undetectable rate [Time frame: 2 years post-treatment initiation.]
• Incidence of Adverse Events (AEs) [Time frame: Throughout the 3-year follow-up period.]
• Serious Adverse Event (SAE) Rate [Time frame: Throughout the 3-year follow-up period.]
• Liver Function Deterioration Rate [Time frame: Throughout the 3-year follow-up period.]
• Quality of Life Change [Time frame: Throughout the 3-year follow-up period.]

Eligibility criteria

Inclusion criteria

• Age: Participants must be between 18 and 70 years of age.
• HBsAg Positive: Participants must be positive for hepatitis B surface antigen (HBsAg).
• Confirmed Hepatocellular Carcinoma (HCC): Participants must have a pathological confirmation of HCC via surgical resection or local ablation.
• BCLC Staging: Participants must have a Barcelona Clinic Liver Cancer (BCLC) staging of 0 or A.
• Liver Function: Participants must have normal or well-compensated liver function, classified as Child-Pugh A.
• Expected Survival: Participants must have an expected survival of more than 3 months.
• Informed Consent: Participants must sign an informed consent form and agree to comply with the study requirements. If a participant is unable to sign the consent form, a legal guardian or agent must do so.

Exclusion criteria

• Prior Systemic Cancer Treatments: Participants who have received prior systemic cancer treatments such as liver transplantation, chemotherapy, targeted therapy, or biological therapy will be excluded.
• Other Active Malignancies: Participants with a history or presence of other active malignancies, except for skin basal cell carcinoma or squamous cell carcinoma that has been cured, or cervical carcinoma in situ, will be excluded.
• Allergies to Interferon: Participants who are allergic to interferon or any of its components, or whom the investigator deems unsuitable for interferon therapy, will be excluded.
• Other Chronic Liver Diseases: Participants with other chronic liver diseases such as hepatitis A, C, D, or E virus infection, alcoholic liver disease, genetic metabolic liver disease, or drug-induced liver disease will be excluded.
• Autoimmune Diseases:Participants with autoimmune diseases,including autoimmune liver disease and psoriasis, will be excluded.
• Severe Liver Dysfunction: Participants with severe liver dysfunction or decompensated cirrhosis will be excluded.
• Renal Impairment: Participants with serum creatinine levels exceeding 1.5 times the upper limit of normal will be excluded.
• Severe Systemic Diseases:Participants with severe systemic diseases affecting the heart,lungs,kidneys,brain,or blood will be excluded.
• Severe Neuropsychiatric Disorders:Participants with severe neuropsychiatric disorders such as epilepsy, depression, mania, or schizophrenia will be excluded.
• Unstable Medical Conditions:Participants with unstable diabetes,hypertension,hyperthyroidism,or other endocrine diseases will be excluded.
• Retinopathy:Participants with a history of severe retinopathy or other evidence of retinopathy will be excluded.
• Substance Abuse:Participants with a history of drug abuse or alcoholism will be excluded.
• Pregnancy or Breastfeeding:Pregnant or breastfeeding women, or women planning to become pregnant during the study period who are unwilling to use contraception, will be excluded.
• Investigator's Judgment:Participants whom the investigator deems unsuitable for the study based on their current medical condition will be excluded.
• Concurrent Participation in Other Trials:Participants who are concurrently involved in other clinical research trials will be excluded.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07120750 · IIT-2024-077

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗