Clinical trial NCT06653127: Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Biliary Tract Cancer Recurrence Surveillance
Official title: Evaluation of Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Minimal Residual Disease (MRD) Assessment and Recurrence Monitoring in Post-treatment Biliary Tract Cancer （BTC）
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Biliary Tract Cancer
Keywords: MRD
ct-mtDNA
recurrence
biliary tract cancer
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2024-10-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will involve patients diagnosed with biliary tract cancer (BTC). The target population for the CCGLC-016 study consists of individuals who meet the following criteria:

Age: Participants must be 18 years of age or older. Diagnosis: Individuals must have a histologically confirmed diagnosis of BTC. 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, visit schedule and any related proceudre.

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 biliary tract cancer.

Detailed description: Biliary tract cancer (BTC) encompasses a range of malignancies including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer. While relatively rare in many high-income countries, it poses a significant health challenge in certain regions, with a rising incidence of intrahepatic cholangiocarcinoma globally. Despite recent therapeutic advancements, BTC remains an aggressive disease with a grim prognosis, characterized by a median overall survival of less than one year and a 5-year survival rate below 5%. 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 BTC. 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 BTC 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 BTC 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 BTC 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 BTC.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed biliary tract cancer (BTC);
* 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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:
measure: Circulating tumor mtDNA (MRD Marker)
timeFrame: Blood samples for MRD marker assessment will be collected at baseline (immediately before treatment) and at 3-7 days post-treatment.
measure: Correlation Between Post-treatment MRD and PFS
timeFrame: 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.
measure: Early Detection of Recurrence Through MRD Monitoring
timeFrame: 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).
measure: Comparison of MRD Detection with Tumor Markers for Early Recurrence Detection
timeFrame: 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.
measure: Comparison of MRD Detection with Imaging for Early Recurrence Detection
timeFrame: 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.
measure: Association of mtDNA Mutational Profile with Clinicopathological Features
timeFrame: The association will be analyzed at baseline and throughout the study duration (up to 2 years), with specific evaluations at 3-month intervals.
measure: Impact of Maintenance Therapy on Negative MRD Detection Rate
timeFrame: 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.
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: Ze-yang Ding, M.D.
role: STUDY_CHAIR
References: