Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in HCC

NCT07350824 | Not Yet Recruiting

• 1 other identifier: CHALLENGE-04
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HCC; Minimal Residual Disease; Recurrence

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Secondary Outcomes (1)

• Overall survival(OS)

  From date of surgery until the date of death from any cause, assessed up to 96 months.

Other Outcomes (1)

• Association between dynamic Minimal Residual Disease (MRD) status and Disease-free survival (DFS)

  From baseline up to 24 months.

Study Arms (2)

Postoperative active monitoring cohort

ACTIVE COMPARATOR

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

Postoperative PD-1 inhibitor adjuvant therapy cohort

EXPERIMENTAL

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

Interventions

Adjuvant PD-1 inhibitors DRUG

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.

Postoperative PD-1 inhibitor adjuvant therapy cohort

Active monitoring OTHER

The patients in the active monitoring cohort only received regular follow-up and MRD testing after the surgery.

Postoperative active monitoring cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years, inclusive, regardless of gender.
• Newly diagnosed, treatment-naïve patients with HCC.
• Received radical treatments, such as liver resection or microwave ablation.
• Combine at least one of the risk factors for tumor recurrence, such as microvascular/macrovascular invasion, poor differentiation, satellite nodules, multiple tumors, and tumor diameter greater than 5 cm.
• Child-Pugh liver function score ≤ 7.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Absence of severe organic diseases affecting the heart, lungs, brain, or other major organs.

You may not qualify if:

• History of other malignancies.
• Recurrent HCC.
• Prior systemic therapy for HCC.
• Unable to complete the follow-up and dynamic MRD monitoring.
• Having an immune deficiency disorder.
• Allergic to PD-1 inhibitors or unable to tolerate related treatments.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

Location

MeSH Terms

Conditions

Neoplasm, Residual; Recurrence

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Central Study Contacts

Wanguang Zhang

CONTACT

13886195965; wgzhang@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 24, 2025
• First Posted: January 20, 2026
• Study Start: December 31, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

CN (1)