Methylation Signature of Circulating Tumour DNA as a Prognostic and Theranostic Tool for Managing Pancreatic Ductal Adenocarcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Sensitivity and Specificity of ctDNA in Early Screening for Pancreatic Cancer
研究概览
简要总结
Developing a characteristic ctDNA methylation panel for pancreatic ductal adenocarcinoma and establishing an intelligent diagnostic and dynamic monitoring model based on ctDNA methylation.
详细描述
Pancreatic cancer is a digestive system malignancy characterized by late clinical detection, high malignancy, and poor prognosis. Exploring economically viable, accurate, and minimally invasive methods for early diagnosis and postoperative monitoring is of significant clinical importance to facilitate early screening and improve patient outcomes. Liquid biopsy, which involves detecting various tumor-related biomarkers in extractable bodily fluids, such as circulating tumor cells, circulating tumor DNA, and exosomes, plays a crucial role in the early diagnosis and prognosis of pancreatic cancer.
Recent research indicates the substantial impact of liquid biopsy in the early diagnosis and prognosis of pancreatic cancer. Differential methylation regions in ctDNA, as opposed to ctDNA mutations, show promise as potential markers. Aberrant DNA methylation has been demonstrated to be more frequent than DNA mutations in tumor development and often occurs early in carcinogenesis. In this project, whole-genome methylation signal scans are conducted on blood samples and tumor tissue samples from pancreatic cancer using next-generation sequencing. The goal is to identify tumor-specific methylation biomarker sites. Subsequently, targeted sequencing is performed on ctDNA based on these identified sites.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients meeting all inclusion criteria are eligible to enter this study, including but not limited to:
- •Age range between 18 and 80 years old;
- •Identification of pancreatic space-occupying lesions through imaging examinations, with a high suspicion of pancreatic malignant tumors and planned for surgical treatment or tissue biopsy for pathological confirmation;
- •According to RECIST 1.1 evaluation criteria, having at least one measurable lesion (the longest diameter of the target lesion on spiral CT scan ≥10mm);
- •Ability to provide tumor tissue and blood samples;
- •Stable vital signs, ECOG score of 0-1;
- •Liver function with AST and ALT ≤ 5 times the upper limit of normal (ULN), Child-Pugh classification of A or B; white blood cell count > 3×10^9/L, absolute neutrophil count ≥ 1.5×10^9/L; platelets ≥ 75×10^9/L; hemoglobin ≥ 90g/L; creatinine clearance rate ≥ 60ml/min; total bilirubin ≤ 3 times ULN;
- •Reproductive-age patients and their spouses willing to adopt contraceptive measures; female patients must undergo a pregnancy test (serum or urine) within 7 days before enrollment with a negative result.
- •Voluntarily participate in this experimental project, patients with good compliance; if the subject is unable to read or sign, the informed consent form must be signed by a legal representative with the subject's informed consent, and for subjects incapable of expressing consent, the introduction and explanation shall be provided to their legal representative, who will then sign the informed consent form.
排除标准
- •Patients meeting any of the exclusion criteria will not be eligible for inclusion, including but not limited to:
- •Unable to provide tumor tissue and blood samples;
- •Previously received molecular targeted therapy, immunotherapy, or anti-tumor radiochemotherapy before this study;
- •History of malignancies other than pancreatic malignancy;
- •Presence of other severe diseases, including but not limited to uncontrolled congestive heart failure (NYHA class III or IV), unstable angina, poorly controlled arrhythmias, uncontrolled moderate to severe hypertension (SBP > 160mmHg or DBP > 100mmHg);
- •Uncontrolled diabetes;
- •Active infection;
- •Patients with active autoimmune diseases requiring long-term use of steroids;
- •Patients who have undergone allogeneic transplantation;
- •Active psychiatric disorders affecting informed consent and/or protocol compliance;
- •Other severe illnesses deemed inappropriate for participation in this study by investigators.
结局指标
主要结局
Sensitivity and Specificity of ctDNA in Early Screening for Pancreatic Cancer
时间窗: Up to 2 years from start of study
Measured using a targeted DNA methylation panel for ctDNA in plasma. The presence or absence of cancer will be confirmed by histopathological diagnosis. Sensitivity and specificity will be calculated using standard diagnostic test evaluation against the gold-standard diagnosis. "Early-stage" is defined as stage I or II pancreatic cancer confirmed by imaging and pathology.
Sensitivity and Specificity of ctDNA Methylation Test for Detection of Postoperative Recurrence
时间窗: Up to 2 years from start of study
Measured using plasma ctDNA methylation profiles collected at scheduled postoperative time points (e.g., every 3 months). Recurrence will be confirmed by imaging (CT/MRI) or biopsy when clinically indicated. Diagnostic accuracy (sensitivity/specificity) will be evaluated by comparing ctDNA results to confirmed recurrence status.
次要结局
- Progression-Free Survival (PFS) Based on Imaging and Clinical Assessment(Up to 3 years from start of study)
- Overall Survival (OS)(Up to 3 years from start of study)
- Early and Late Imaging Data(Up to 3 years from start of study)
- Levels of Serum Tumor Biomarkers (CA19-9, CEA) in Early-Stage Pancreatic Cancer(Up to 3 years from start of study)
研究者
Yingbin Liu, MD, PhD, FACS
principal investigator
Shanghai Jiao Tong University School of Medicine