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NCT Number: NCT06653127

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. 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 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.

Secondary outcomes

  1. 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.

    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 post-treatment). 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.

  2. 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.

    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.

  3. 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).

    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.

  4. 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.

    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 (CEA, CA19-9) to determine which method can detect recurrence sooner.

  5. 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.

    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.

  6. 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.

    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.

  7. 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.

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Han Gao

CONTACT

[email protected]

+8617730117747

Ze-yang Ding, M.D.

CONTACT

[email protected]

+8613407156200

Sponsors and collaborators

Lead sponsor

Tongji Hospital

Other

Registry information

Official study 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）

Acronym: CCGLC-016

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Oct 22, 2024
Registry last updated
Dec 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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