GNB4 and Riplet Gene Methylation Combined Detection Kit for Hepatocellular Carcinoma Recurrence Monitoring

Official title

A Prospective, Multicenter Observational Clinical Study of the GNB4 and Riplet Gene Methylation Combined Detection Kit (Real-time PCR) for Post-treatment Recurrence Monitoring in Hepatocellular Carcinoma

Overview

This is a prospective, multicenter, observational longitudinal study designed to evaluate the clinical performance of the GNB4 and Riplet Gene Methylation Combined Detection Kit (Real-time PCR) for monitoring recurrence after treatment of hepatocellular carcinoma. Adult patients with confirmed or highly suspected hepatocellular carcinoma who are planned to undergo, or have undergone, liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE) will be enrolled. Plasma samples will be collected before treatment and during follow-up after treatment. The test results of the study kit will be compared with the clinical reference standard, which is based on comprehensive clinical diagnosis according to routine practice and relevant guidelines. The study aims to assess whether this methylation-based blood test can help identify recurrence of hepatocellular carcinoma after treatment. The main clinical performance measures include sensitivity in patients with recurrent disease, specificity in patients without recurrence, and overall agreement with the clinical reference standard.

Detailed description

Hepatocellular carcinoma (HCC) has a high risk of recurrence after treatment, and effective post-treatment monitoring is important for early detection and clinical management. This study is designed to evaluate the clinical effectiveness of the GNB4 and Riplet Gene Methylation Combined Detection Kit (Real-time PCR) for recurrence monitoring in patients with primary hepatocellular carcinoma after treatment.

This is a prospective, multicenter, observational longitudinal study. Eligible participants are adults aged 18 years or older with confirmed or highly suspected HCC who are scheduled to receive, or have already received, one or more of the following treatments: liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE). Patients will be followed according to routine clinical practice and relevant guideline recommendations.

Human plasma samples will be collected for testing with the study device. Samples may be obtained before treatment and at follow-up visits after treatment. The assay result from the GNB4 and Riplet methylation test will be compared in a blinded manner with the clinical reference standard. The clinical reference standard is the investigator's comprehensive assessment of recurrence status based on clinical evaluation, imaging, laboratory findings, and applicable diagnostic guidelines.

The primary purpose of the study is to evaluate the clinical performance of the study kit for identifying recurrence after treatment of HCC. Key performance measures include sensitivity for recurrent HCC, specificity for non-recurrent cases, overall agreement, and corresponding 95% confidence intervals. Participants with recurrence or metastasis may complete follow-up at the time recurrence is confirmed, while participants without recurrence will be followed for at least 6 months after initial treatment, with possible extension according to the protocol and clinical practice.

This study is intended to support clinical evaluation of the assay as a blood-based tool for post-treatment recurrence monitoring in hepatocellular carcinoma.

Interventions

• Diagnostic test GNB4 and Riplet Gene Methylation Combined Detection Kit (Real-time PCR)
  An in vitro qualitative real-time PCR assay used to detect methylation of the GNB4 and Riplet genes in circulating cell-free DNA (cfDNA) from human plasma samples. In this study, the assay is used for post-treatment recurrence monitoring in patients with hepatocellular carcinoma after liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE). Test results are compared with the clinical reference standard based on comprehensive clinical diagnosis during follow-up

Primary outcome measures

• Sensitivity for recurrent hepatocellular carcinoma [Time frame: At the end of follow-up, up to 12 months after treatment]
• Specificity for non-recurrent hepatocellular carcinoma [Time frame: At the end of follow-up, up to 12 months after treatment]
• Overall agreement with the clinical reference standard [Time frame: At the end of follow-up, up to 12 months after treatment]

Eligibility criteria

Inclusion criteria

Participants must meet criterion (1) and any one of criteria (2) through (4):

• Adults aged 18 years or older;
• Patients with confirmed hepatocellular carcinoma or highly suspected hepatocellular carcinoma who are planned to undergo one or more of the following treatments: liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE);
• Patients who have previously received antitumor therapy but remain in a tumor-bearing state of hepatocellular carcinoma and are planned to undergo one or more of the following treatments: liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE);
• Post-treatment patients with primary hepatocellular carcinoma who have already undergone one or more of the following treatments: liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE), and whose result of the study assay before treatment was positive.

Exclusion criteria

• Patients with hepatocellular carcinoma who will not undergo any of the following treatments: liver resection, liver transplantation, ablation, or transarterial chemoembolization (TACE);
• Patients enrolled as highly suspected hepatocellular carcinoma whose final diagnosis according to the clinical reference standard is not primary hepatocellular carcinoma, or for whom it cannot be determined whether the disease is primary hepatocellular carcinoma;
• Patients whose samples collected before hepatocellular carcinoma treatment were not stored in accordance with protocol requirements;
• Patients whose samples collected before hepatocellular carcinoma treatment are insufficient in volume to meet the testing requirements.

Any enrolled participant who is subsequently excluded from the clinical study will be documented, and the reason for exclusion will be clearly recorded.

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.

Publications

• Guo DZ, Huang A, Wang YC, Zhou S, Wang H, Xing XL, Zhang SY, Cheng JW, Xie KH, Yang QC, Ma CC, Li Q, Chen Y, Su ZX, Fan J, Liu R, Liu XL, Zhou J, Yang XR. Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study. Clin Transl Med. 2024 May;14(5):e1652. doi: 10.1002/ctm2.1652. PMID 38741204
• Tsilimigras DI, Bagante F, Sahara K, Moris D, Hyer JM, Wu L, Ratti F, Marques HP, Soubrane O, Paredes AZ, Lam V, Poultsides GA, Popescu I, Alexandrescu S, Martel G, Workneh A, Guglielmi A, Hugh T, Aldrighetti L, Endo I, Pawlik TM. Prognosis After Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classificati PMID 31267302
• Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, Bonaventure A, Valkov M, Johnson CJ, Esteve J, Ogunbiyi OJ, Azevedo E Silva G, Chen WQ, Eser S, Engholm G, Stiller CA, Monnereau A, Woods RR, Visser O, Lim GH, Aitken J, Weir HK, Coleman MP; CONCORD Working Group. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patie PMID 29395269
• Pizzato M, Li M, Vignat J, Laversanne M, Singh D, La Vecchia C, Vaccarella S. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet Diabetes Endocrinol. 2022 Apr;10(4):264-272. doi: 10.1016/S2213-8587(22)00035-3. Epub 2022 Mar 7. PMID 35271818

Identifiers

NCT: NCT07489768 · 2025-S281

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗