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）
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Patients with other active tumors or severe complications;
- •Insufficient tumor tissue for MRD detection.
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: 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.
次要结局
- 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.)
- 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.)
- 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.)