An interventional study of Adjuvant PD-1 inhibitors and Active monitoring in HCC, Minimal Residual Disease and Recurrence, sponsored by Tongji Hospital. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-01-20.
Sponsored by Tongji Hospital · Not applicable, Interventional, and Treatment
Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. While curative resection is pivotal, high postoperative recurrence rates remain a major challenge. Adjuvant immune checkpoint inhibitors (ICIs) show promise in improving outcomes, but biomarkers to identify patients who will benefit are lacking. Current clinicopathological risk factors for minimal residual disease (MRD) are suboptimal in sensitivity and specificity.
Circulating tumor DNA (ctDNA) analysis, reflecting real-time tumor dynamics, offers a promising approach for MRD detection. This study focuses on the methylation status of GNB4 and Riplet-genes located within HCC-associated CpG islands-using a bespoke bisulfite-conversion and qPCR assay to sensitively detect methylated alleles, thereby enabling MRD monitoring.
To clinically validate this approach, we will conduct a prospective, multicenter cohort study assessing the predictive value of serial *GNB4/Riplet* methylation testing for recurrence and adjuvant therapy benefit.
Hepatocellular carcinoma (HCC) is a leading global malignancy and a primary cause of mortality in patients with chronic liver disease. While curative resection offers a critical treatment strategy, postoperative recurrence remains a major obstacle. Emerging evidence suggests adjuvant therapy with immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 inhibitors, may improve disease-free survival; however, identifying the patient subgroup most likely to benefit remains challenging. Theoretically, patients at high risk for minimal residual disease (MRD) post-surgery represent the ideal target for adjuvant treatment. Current clinical practice relies on indirect pathological surrogates of MRD-such as microvascular invasion, poor differentiation, or satellite nodules-which lack sufficient sensitivity and specificity.
Cell-free DNA (cfDNA), with its short half-life, dynamically mirrors tumor evolution, making it a promising tool for monitoring recurrence. The genes GNB4 and Riplet are located within CpG islands strongly associated with hepatocarcinogenesis. We developed specific primers and fluorescent probes targeting their bisulfite-converted sequences to enable selective PCR-based detection of methylated alleles. Monitoring MRD via *GNB4/Riplet* methylation status thus offers a potential method for dynamic assessment of tumor progression and recurrence, optimizing patient risk stratification and guiding therapeutic decisions.
To evaluate this approach, we will conduct a prospective, multi-center cohort study to investigate the predictive value of MRD for recurrence and adjuvant therapy benefit. The study comprises two cohorts: 1) an Active Surveillance Cohort, undergoing a pre-operative MRD assessment followed by regular post-operative surveillance and serial MRD testing; and 2) an Adjuvant Therapy Cohort, receiving pre-operative MRD assessment followed by standard adjuvant PD-1 inhibitor therapy alongside serial MRD monitoring. This study aims to validate a more effective tool for predicting recurrence and to identify patients most likely to benefit from adjuvant immunotherapy.
263 studies on the registry are indexed under Neoplasm, Residual; 120 are open to participants now.
This study's planned enrollment of 276 is above the median of 46 across 167 interventional studies indexed under Neoplasm, Residual.
Browse Neoplasm, Residual studies →Tongji Hospital is the lead sponsor of 373 studies on the registry; 204 are open to participants now.
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Exclusion Criteria:
The postoperative active monitoring cohort collected a single blood sample for MRD monitoring before the surgery, and then dynamically collected blood samples for MRD monitoring at each follow-up visit after the surgery. This cohort only received active monitoring after the surgery.
Other: Active monitoring
The postoperative PD-1 inhibitor-adjuvant cohort collected one blood sample for MRD monitoring before surgery, and dynamically collected blood samples for MRD monitoring at each follow-up visit after surgery. This cohort received only regular PD-1 inhibitor-assisted treatment after surgery.
Drug: Adjuvant PD-1 inhibitors
The patients in the postoperative adjuvant treatment cohort received regular PD-1 inhibitor adjuvant therapy (Sintilimab), once every 21 days, for a total of 8 times, and undergoing dynamic MRD testing.
The patients in the active monitoring cohort only received regular follow-up and MRD testing after the surgery.
Disease-free survival(DFS)
DFS is defined as the time from surgery to the first recurrence. The difference in DFS between the two cohorts is compared.
Time frame: From date of surgery until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.
Overall survival(OS)
OS is defined as the time from surgery to the date of death.
Time frame: From date of surgery until the date of death from any cause, assessed up to 96 months.
Association between dynamic Minimal Residual Disease (MRD) status and Disease-free survival (DFS)
The predictive efficacy of dynamic MRD monitoring for recurrence. MRD will be assessed in peripheral blood samples at specified time points. The association between MRD status (positive/negative) and DFS will be quantified using Cox proportional hazards regression. The primary analysis will evaluate the hazard ratio for recurrence or death in MRD-positive vs. MRD-negative participants.
Time frame: From baseline up to 24 months.
This study is not yet recruiting, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
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Tongji Hospital