HCCNCT07350824
Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in HCC
A study testing Adjuvant PD-1 inhibitors and Active monitoring in people with HCC and Minimal Residual Disease, run by Tongji Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HCC, Minimal Residual Disease, Recurrence
- What is being tested?
- Adjuvant PD-1 inhibitors and Active monitoring
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 276 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2025to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Division of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
About this study
Official title: Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in Hepatocellular Carcinoma: A Prospective, Multicenter Study
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.
Read the detailed description
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.
- Conditions
- HCC, Minimal Residual Disease, Recurrence
- Being tested
- Adjuvant PD-1 inhibitors, Active monitoring
- Medical subject headings
- Neoplasm, Residual, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adjuvant PD-1 inhibitorsDrug
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.
Active monitoringOther
The patients in the active monitoring cohort only received regular follow-up and MRD testing after the surgery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Adjuvant PD-1 inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
OS is defined as the time from surgery to the date of death.
Measured: From date of surgery until the date of death from any cause, assessed up to 96 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2026
- Study start31 Dec 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HCCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wan-Guang Zhang, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07350824
- Sponsor's protocol ID
- CHALLENGE-04
- Status last verified
- Jan 2026
- First submitted
- 24 Dec 2025
- Last updated
- 20 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in Hepatocellular Carcinoma: A Prospective, Multicenter Study
- ClinicalTrials.gov ID
- NCT07350824
- Acronym / sponsor ID
- CHALLENGE-04
- Conditions
- HCC, Minimal Residual Disease, Recurrence
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 31 Dec 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 20 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Postoperative active monitoring cohort | Active comparator | Other: Active monitoringThe 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. |
| Postoperative PD-1 inhibitor adjuvant therapy cohort | Experimental | Drug: Adjuvant PD-1 inhibitorsThe 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adjuvant PD-1 inhibitorsThe 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. | Drug | Postoperative PD-1 inhibitor adjuvant therapy cohort |
| Active monitoringThe patients in the active monitoring cohort only received regular follow-up and MRD testing after the surgery. | Other | Postoperative active monitoring cohort |
Primary outcome
Disease-free survival(DFS)
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.
DFS is defined as the time from surgery to the first recurrence. The difference in DFS between the two cohorts is compared.
1 secondary outcome
Overall survival(OS)
Time frame: From date of surgery until the date of death from any cause, assessed up to 96 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Adjuvant PD-1 inhibitors and Active monitoring in people with HCC and Minimal Residual Disease, run by Tongji Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wanguang Zhang (13886195965, wgzhang@tjh.tjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival(DFS) (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026; AzTrials last refreshed its copy on 26 Oct 2026.