Hepatocellular Carcinoma (HCC)CCGLC-015NCT06653062
Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Hepatocellular Carcinoma Recurrence Surveillance
An observational study of Hepatocellular Carcinoma (HCC), run by Tongji Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Plasma and Tumor Tissue Mitochondrial DNA (mtDNA) Mutation Analysis
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 18 Nov 2024to 1 Jun 2028
- How long will I take part?
- 2 Years
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study will involve patients diagnosed with hepatocellular carcinoma (HCC) . The target population for the CCGLC-015 study consists of individuals who meet the following criteria: Age: Participants must be 18 years of age or older. Diagnosis: Individuals must have a confirmed diagnosis of HCC. Prognosis: Patients are expected to have a life expectancy of at least 12 weeks, indicating a reasonable prospect for survival following study enrollment. Informed Consent: All participants or their legally authorized representatives must provide written informed consent. This ensures they are fully aware of the study, objectives, procedures, potential risks, and benefits, and are willing to comply with the study protocol. Compliance: Participants must be capable of and agree to adhere to the study\'s visit schedule and any related procedure.
Who may be able to join
- 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.
Who cannot join
- Patients with other active tumors or severe complications;
- Insufficient tumor tissue for MRD detection.
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, 1 recruiting
- Recruiting
Tongji Hospital
Wuhan, Hubei, 430030
Ze yang Ding, M.D., +86 13407156200, zyding@tjh.tjmu.edu.cn
Han Gao, +8617730117747, gh1023606887@163.com
About this study
Official title: Evaluation of Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Minimal Residual Disease (MRD) Assessment and Recurrence Monitoring in Hepatocellular Carcinoma (HCC)
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.
Read the 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.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Plasma and Tumor Tissue Mitochondrial DNA (mtDNA) Mutation Analysis
- Keywords
- MRD, ct-mtDNA, recurrence, hepatocellular carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma and Tumor Tissue Mitochondrial DNA (mtDNA) Mutation AnalysisOther
Targeted Analysis of Mitochondrial Mutations: Unlike many interventions that may focus on nuclear DNA or general tumor markers, this intervention specifically analyzes mutations within the mitochondrial genome. This focus on mtDNA is based on evidence suggesting that mtDNA mutations are more frequent and may serve as more sensitive indicators of minimal residual disease (MRD) in cancer patients.
Liquid Biopsy Approach: The intervention utilizes a liquid biopsy technique, which involves the collection and analysis of peripheral blood samples to detect circulating tumor DNA (ctDNA). This non-invasive method contrasts with traditional tissue biopsy interventions, offering a less intrusive approach to monitor disease progression and recurrence.
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
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.
Measured: 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.
Secondary outcomes (7)
Circulating tumor mtDNA (MRD Marker)
This secondary outcome measure aims to assess changes in MRD markers before treatment and at a specific time point shortly after treatment (3-7 days). The analysis will determine the immediate impact of medical intervention on the levels of circulating tumor mtDNA, providing insights into the effectiveness of treatment in removing or reducing MRD.
Measured: 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
This secondary outcome measure will analyze the relationship between the quantity of residual tumor molecular burden, as detected by MRD testing, and the length of progression-free survival. The goal is to determine if a higher molecular burden of residual disease is associated with shorter PFS.
Measured: 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
The study will evaluate the ability of MRD detection, based on plasma tumor mtDNA mutations, to predict disease recurrence earlier than traditional tumor markers or imaging methods. This comparison will involve monitoring ctDNA levels over the two-year post-treatment period and comparing the timing of abnormal rises in ctDNA to the detection of recurrence by other means.
Measured: 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
This outcome measure will specifically compare the timing of increases in circulating tumor DNA (ctDNA) levels, as detected by MRD testing, to the rises in serum tumor markers (AFP, PIVKA-II) to determine which method can detect recurrence sooner.
Measured: 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
The study will evaluate whether increases in ctDNA levels, as detected by MRD testing, precede objective disease progression detected by imaging methods, thus serving as an earlier indicator of recurrent disease.
Measured: 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
An exploratory analysis will investigate whether specific mtDNA mutational profiles are associated with certain clinicopathological features of the cancer, such as tumor size, differentiation, or stage.
Measured: 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
The study will explore whether patients receiving maintenance therapy after the initial treatment phase have a higher rate of negative MRD detection, suggesting a potential role of MRD in guiding therapeutic decisions.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study start18 Nov 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Tongji HospitalThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ze-yang Ding, MD, Tongji Hospital
- Investigators
- Ze-yang Ding, M.D., Study chair, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06653062
- Sponsor's protocol ID
- TJ-IRB202407116
- Acronym
- CCGLC-015
- Status last verified
- Dec 2024
- First submitted
- 8 Oct 2024
- Last updated
- 30 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Minimal Residual Disease (MRD) Assessment and Recurrence Monitoring in Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT06653062
- Acronym / sponsor ID
- CCGLC-015 / TJ-IRB202407116
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- MRD, ct-mtDNA, recurrence, hepatocellular carcinoma
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 18 Nov 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 22 Oct 2024 (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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study will involve patients diagnosed with hepatocellular carcinoma (HCC) . The target population for the CCGLC-015 study consists of individuals who meet the following criteria: Age: Participants must be 18 years of age or older. Diagnosis: Individuals must have a confirmed diagnosis of HCC. Prognosis: Patients are expected to have a life expectancy of at least 12 weeks, indicating a reasonable prospect for survival following study enrollment. Informed Consent: All participants or their legally authorized representatives must provide written informed consent. This ensures they are fully aware of the study, objectives, procedures, potential risks, and benefits, and are willing to comply with the study protocol. Compliance: Participants must be capable of and agree to adhere to the study\'s visit schedule and any related procedure.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- Patients with other active tumors or severe complications;
- Insufficient tumor tissue for MRD detection.
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 |
|---|---|---|
| Plasma and Tumor Tissue Mitochondrial DNA (mtDNA) Mutation AnalysisTargeted Analysis of Mitochondrial Mutations: Unlike many interventions that may focus on nuclear DNA or general tumor markers, this intervention specifically analyzes mutations within the mitochondrial genome. This focus on mtDNA is based on evidence suggesting that mtDNA mutations are more frequent and may serve as more sensitive indicators of minimal residual disease (MRD) in cancer patients. Liquid Biopsy Approach: The intervention utilizes a liquid biopsy technique, which involves the collection and analysis of peripheral blood samples to detect circulating tumor DNA (ctDNA). This non-invasive method contrasts with traditional tissue biopsy interventions, offering a less intrusive approach to monitor disease progression and recurrence. | Other | – |
Primary outcome
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.
7 secondary outcomes
Circulating tumor mtDNA (MRD Marker)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
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 30 Dec 2024.
- Individual participant dataSharing planned: Undecided
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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.
Ze-yang Ding, M.D. study chair
Tongji Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma (HCC), 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 5 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 30 Dec 2024. 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 Ze-yang Ding, M.D. (+8613407156200, zyding@tjh.tjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). 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 30 Dec 2024.