Application and Exploration of Personalized ctDNA-MRD Detection Technology in Predicting the Efficacy of Neoadjuvant Therapy for Rectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Complete Response (CR) rate
研究概览
简要总结
This study is a single-center, prospective, observational clinical trial enrolling patients with locally advanced rectal cancer (cT3-4aN0M0 and cT1-4aN1-2M0). By collecting tissue and blood samples at multiple timepoints, and integrating multi-omics data including ctDNA mutations, copy number variations, and mtDNA profiles, a multi-omics model will be constructed to predict the efficacy of neoadjuvant therapy for rectal cancer.
详细描述
This study is a single-center, prospective, observational clinical trial designed to construct and validate a multi-omics-based predictive model for neoadjuvant treatment efficacy in locally advanced rectal cancer. Patients diagnosed with locally advanced rectal cancer (cT3-4aN0M0 and cT1-4aN1-2M0) are enrolled, and tissue and blood samples are dynamically collected at multiple time points. By simultaneously analyzing plasma circulating tumor DNA (ctDNA) somatic mutations, copy number variations, and mitochondrial DNA (mtDNA), a multi-dimensional molecular biomarker system is constructed.The primary objectives of the study include: first, prospectively validating the efficacy of a multi-dimensional molecular biomarker model based on ctDNA mutations, mtDNA, and copy number variations for detecting molecular residual disease (MRD) during neoadjuvant therapy and assessing its sensitivity and specificity in predicting pathological response; second, comparing the sensitivity and specificity of different omics features-ctDNA mutations, mtDNA, copy number variations, alone or in combination-in predicting treatment efficacy after surgery.The secondary objectives are: first, to construct a multi-omics model integrating ctDNA mutations, copy number variations, and mtDNA for dynamically assessing tumor burden changes during neoadjuvant therapy; second, to explore and optimize ctDNA-MRD detection technology, aiming to overcome the high sample volume requirements of traditional methods and improve the detection rate of low-abundance ctDNA.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1: Signed a written informed consent form and voluntarily participated in this study
- •2: Aged 18-75 years, regardless of sex
- •3: Histopathologically confirmed rectal adenocarcinoma
- •4: Clinical stage II-III as assessed by MRI (according to the AJCC 8th edition)
- •5: Distance from the lower tumor margin to the anal verge ≤10 cm
- •6: Surgically resectable
- •7: Able to swallow tablets normally
- •8: ECOG PS 0-1
- •9: No prior antitumor therapy for rectal cancer, including radiotherapy, chemotherapy, or surgery
- •10: Scheduled to undergo surgical treatment after completion of neoadjuvant therapy
- •11: No surgical contraindications
- •12: Normal function of major organs, including: complete blood count, blood biochemistry, and coagulation function
排除标准
- •1: History of allergy to monoclonal antibodies, any component of tislelizumab, or capecitabine
- •2: Prior or ongoing receipt of any tumor-directed surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc
- •3: Presence of any active autoimmune disease or history of autoimmune disease
- •4: History of immunodeficiency, including a positive HIV test result, other acquired or congenital immunodeficiency disorders, or history of organ transplantation or allogeneic bone marrow transplantation
- •5: Poorly controlled cardiac clinical symptoms or diseases, including but not limited to: heart failure of NYHA class II or above, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmia that remains poorly controlled without or despite clinical intervention
- •6: Diagnosis of another malignancy within 5 years prior to the first use of the study drug, except for malignancies with low risk of metastasis or death (5-year survival rate >90%), such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, which may be considered for inclusion
- •7: Pregnant or lactating women
- •8: Other factors, as judged by the investigator, that may lead to premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring concomitant treatment, alcohol abuse, drug abuse, family or social factors, or any condition that may affect the safety or compliance of the participant
研究组 & 干预措施
Rectal Cancer ctDNA-MRD Detection Cohort
This study is an exploratory study, with an expected enrollment of 60 patients diagnosed with stage II-III rectal cancer who are scheduled to undergo neoadjuvant therapy. The sample collection and testing procedures are as follows: Before neoadjuvant therapy: Baseline endoscopic biopsy tissue or paraffin sections:1.1 Two pieces of endoscopic biopsy tissue, approximately 2 mm in diameter, are collected and placed in tissue preservation tubes.1.2 Ten unstained tissue slides are prepared. Peripheral blood collection: 10 mL of blood is collected using cell-free DNA blood collection tubes for the following assays:① ctDNA-customized MRD high-depth sequencing;② ctDNA shallow whole-genome sequencing (sWGS) for monitoring copy number variation (CNV) profiles;③ Mitochondrial DNA (mtDNA) analysis. During neoadjuvant therapy (within 2 weeks after radiotherapy completion): Peripheral blood collection: 10 mL of blood is collected using cell-free DNA blood collection tubes for the followin
干预措施: Personalized ctDNA-MRD Detection (Diagnostic Test)
结局指标
主要结局
Complete Response (CR) rate
时间窗: Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion)
The proportion of patients confirmed to have achieved complete response after neoadjuvant therapy, as assessed by endoscopy, imaging (pelvic MRI/chest-abdominal CT), digital rectal examination, and pathological evaluation. The assessment time point corresponds to T2 (8-14 weeks after the end of neoadjuvant therapy). Complete response requires: normal mucosa on endoscopy with negative biopsy; no residual tumor on imaging; no palpable mass on digital rectal examination; and no viable tumor cells in postoperative pathology (if surgery is performed).
次要结局
- Complete Response Rate (CR)(Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion))
- Major Pathological Response Rate (MPR)(1 month after surgery)
- Objective Response Rate (ORR)(Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion))
- Disease-Free Survival (DFS)(Monitoring Period: Every 3 or 6 months after treatment completion, continued until 1 year.)
- Overall Survival (OS)(From the randomization date to the date of death from any cause, disease recurrence, or metastasis-whichever occurred first-assessed over the entire study period with a planned maximum follow-up of 12 months.)
- Organ Preservation Rate (OPR)(1 month after surgery)
- Neoadjuvant Therapy Score for Rectal Cancer (NAR)(Post-neoadjuvant Therapy Efficacy Assessment Time Point (within 8-12 weeks after radiotherapy completion))
- Quality of Life (QoL)(Baseline (T0), within 2 weeks after completion of radiotherapy (T1), 8-12 weeks after completion of radiotherapy (T2), and 4 weeks after surgery or after final treatment regimen determination (T3), through study completion, an average of 1 year)
研究者
Yao Hongwei
Professor
Beijing Friendship Hospital