Circulating Tumor Mitochondrial DNA (ct-mtDNA) As a Biomarker for Biliary Tract Cancer Recurrence Surveillance

NCT06653127 | Recruiting DMC

• 1 other identifier: TJ-IRB202407115
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Biliary Tract Cancer

Keywords

MRD; ct-mtDNA; recurrence; biliary tract cancer

Outcome Measures

Primary Outcomes (1)

• 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 medical treatment for biliary tract cancer. 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.

  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)

  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.

Interventions

Plasma and Tumor Tissue Mitochondrial DNA (mtDNA) Mutation Analysis OTHER

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.

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Patients with other active tumors or severe complications;
• Insufficient tumor tissue for MRD detection.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430030, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma Samples: Peripheral blood samples collected in EDTA anticoagulant tubes will be processed to separate plasma and blood cells within 4 to 8 hours, optimally within 4 hours post-collection. Plasma samples are stored at -20°C to preserve the integrity of circulating tumor DNA (ctDNA) and other biomarkers. Blood Cell Samples: Blood cells separated from the plasma are also stored at -20°C for potential future analysis, including but not limited to, complete blood count, differential analysis, and other cellular markers. Tumor Tissue Samples: Tumor tissue samples collected during surgery and biopsy will be preserved to allow for genetic and molecular analysis. These samples are crucial for identifying tumor-specific mitochondrial mutations. Tissue samples are stored in liquid nitrogen tanks or at -70°C to maintain their molecular integrity.

MeSH Terms

Conditions

Biliary Tract Neoplasms; Recurrence

Interventions

DNA, Mitochondrial

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DNA, Circular; DNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ze-yang Ding, M.D.

  Tongji Hospital

  STUDY CHAIR

Central Study Contacts

Ze-yang Ding, M.D.

CONTACT

+8613407156200; zyding@tjh.tjmu.edu.cn

Han Gao

CONTACT

+8617730117747; gh1023606887@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: October 22, 2024
• Study Start: November 13, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 30, 2024

Record last verified: 2024-12

Locations

CN (1)