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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 332
- 主要终点
- 3-Year Cumulative Recurrence Rate via MRI (LI-RADS)
研究概览
简要总结
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.
详细描述
- 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.
- 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
- 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.
- 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
3-Year Cumulative Recurrence Rate via MRI (LI-RADS)
时间窗: 3 years post-radical treatment.
1. Measurement Tool: Liver Imaging Reporting and Data System (LI-RADS v2018) 1.1 Primary modality: Dynamic contrast-enhanced MRI 1.2 Confirmatory criteria: 1.2.1 LI-RADS 5 (definite HCC): 1.2.1.1 Arterial hyperenhancement + 1.2.1.2 Portal venous washout ± 1.2.1.3 Capsule/threshold growth 1.2.2 Histopathology (biopsy) for equivocal cases 2. Definition: Proportion of participants with new intrahepatic lesions meeting LI-RADS 5 criteria or histologically confirmed HCC metastases within 3 years post-radical treatment. 3. Clinical Significance: Recurrence defined as: 3.1 Local (original site) 3.2 Intrahepatic (\>2 cm from resection margin) 3.3 Extrahepatic (metastases with biopsy confirmation)
次要结局
- 2-Year HBsAg Seroclearance Rate(2 years post-treatment initiation.)
- 2-Year HBV DNA undetectable rate(2 years post-treatment initiation.)
- Incidence of Adverse Events (AEs)(Throughout the 3-year follow-up period.)
- Serious Adverse Event (SAE) Rate(Throughout the 3-year follow-up period.)
- Liver Function Deterioration Rate(Throughout the 3-year follow-up period.)
- Quality of Life Change(Throughout the 3-year follow-up period.)