Evaluation of Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Minimal Residual Disease (MRD) Assessment and Recurrence Monitoring in Hepatocellular Carcinoma (HCC)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Tongji Hospital
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Progression-Free Survival (PFS)
Study Overview
Brief Summary
This is a prospective, observational, single-center study. The purpose of this study is to evaluate the efficacy of circulating tumor mitochondrial DNA (ct-mtDNA) in plasma as a biomarker for minimal residual disease (MRD) assessment and recurrence monitoring in patients with hepatocellular carcinoma.
Detailed Description
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with a significant proportion of cases occurring in China. Despite advancements in treatment, the prognosis for HCC remains poor due to late diagnosis and high recurrence rates. Minimal Residual Disease (MRD) refers to the presence of residual cancer cells after treatment, which can lead to tumor recurrence. The primary objective of this study is to evaluate the effectiveness of plasma tumor mitochondrial mutations as a biomarker for MRD assessment and recurrence monitoring in patients with HCC. The study hypothesizes that the presence and dynamics of tumor mitochondrial mutations in plasma are associated with the risk of recurrence and overall survival in HCC patients. This is a prospective, observational, single-center study conducted by the Chinese Cooperative Group of Liver Cancer (CCGLC) under the auspices of the Chinese Chapter of International Hepato-Pancreato Biliary Association. The study will involve the collection and analysis of plasma samples from patients with HCC to detect ct-mtDNA mutations before and after treatment. The primary clinical endpoint is the impact of MRD status on progression-free survival (PFS). Secondary endpoints include the influence of treatment on MRD markers, the correlation between post-treatment residual tumor molecular burden and PFS, and the ability of MRD detection to predict recurrence earlier than traditional tumor markers or imaging methods. This study seeks to contribute to the field of HCC management by providing a more precise and personalized approach to MRD assessment and recurrence monitoring. The findings have the potential to improve long-term treatment outcomes and quality of life for patients with HCC.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with hepatocellular carcinoma (HCC);
- •Diagnosis of HCC is according to the American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines of HCC management;
- •At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or mRESIST criteria.;
- •Expected survival time of 12 weeks or more;
- •Signed informed consent form and ability to comply with the study visits and related procedures as stipulated in the protocol.
Exclusion Criteria
- •Patients with other active tumors or severe complications;
- •Insufficient tumor tissue for MRD detection.
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: PFS will be assessed from baseline (initiation treatment date) to the first occurrence of disease progression or death, with follow-up assessments at regular intervals up to 2 years post-treatment.
The primary outcome measure of this study is to evaluate the effect of minimal residual disease (MRD) status, as identified by the presence of tumor mitochondrial DNA (mtDNA) mutations in plasma, on the progression-free survival of patients after treatment for hepatocellular carcinoma. Progression-free survival is defined as the time from the initiation of treatment to the first occurrence of disease progression or death due to any cause, as determined by imaging studies following RECIST 1.1 criteria.
Secondary Outcomes
- Circulating tumor mtDNA (MRD Marker)(Blood samples for MRD marker assessment will be collected at baseline (immediately before treatment) and at 3-7 days post-treatment.)
- Correlation Between Post-treatment MRD and PFS(Residual tumor molecular burden will be assessed at the time of post-treatment blood sample collection (3-7 days post-treatment), with PFS being measured from baseline to the first occurrence of disease progression or death, up to 2 years post-treatment.)
- Early Detection of Recurrence Through MRD Monitoring(MRD monitoring will be conducted at regular intervals post-treatment, with the earliest detection of recurrence being the primary focus within the two-year follow-up period (e.g., every 3 months).)
- Comparison of MRD Detection with Tumor Markers for Early Recurrence Detection(Tumor marker levels and MRD status will be assessed at 3-month intervals post-treatment for up to two years, with the timing of abnormal rises being the critical comparison point.)
- Comparison of MRD Detection with Imaging for Early Recurrence Detection(Imaging for disease progression will be performed at 3-month intervals or as clinically indicated (up to 2 years), with ctDNA levels being monitored in parallel to determine the lead time of MRD detection over imaging.)
- Association of mtDNA Mutational Profile with Clinicopathological Features(The association will be analyzed at baseline and throughout the study duration (up to 2 years), with specific evaluations at 3-month intervals.)
- Impact of Maintenance Therapy on Negative MRD Detection Rate(Assessment of the impact of maintenance therapy on MRD detection rate will be conducted at follow-up visits where MRD testing is performed at 6-month intervals after the initial treatment phase for up to two years.)
Investigators
Ze-yang Ding, MD
Prof.
Tongji Hospital