Personalized Multimodal Treatment for Resectable Esophageal Cancer by Detecting Minimal Residual Disease Using Circulating Tumor DNA: a Multicentric Prospective Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 248
- 试验地点
- 6
- 主要终点
- To correlate the presence of minimal residual disease after resection as assessed by ctDNA with disease recurrence.
研究概览
简要总结
Purpose of this study is to determine the value of liquid biopsies, e.g. testing of minimal residual disease (MRD) by using liquid biopsies to measure circulating tumour DNA (ctDNA) at diagnosis and during the multimodal and multidisciplinary curative-intent treatment of resectable esophageal cancer.
详细描述
Multicentric, retrospective and prospective components.
Retrospective collection of leftover tissue from standard of care biopsies or resection specimens and prospective collection of additional blood samples for study-specific analyses at specific timepoints, at the same time as routine labs are foreseen. No additional venipunctures are expected.
Three distinct patient groups are defined, depending on the therapeutic scenario patients undertake:
Scenario 1: primary resection then follow-up - Study-specific liquid biopsies will be collected in 98 patients, at the time of routine labs. Samples will be acquired before resection, at 6-8 weeks, 6 and 12 months after resection.
Scenario 2: chemoradiation followed by resection and follow-up - Study-specific liquid biopsies will be collected in 50 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks, 6 and 12 months after surgery. A subgroup of patients will undertake adjuvant immunotherapy and will constitute Group 3. Timing of sampling will be adjusted accordingly as per study flowcharts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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
- •Male or female, age > 18 years
- •New diagnosis of esophageal cancer, pathologically confirmed squamous cell carcinoma (ESCC) or adenocarcinoma (EAC)
- •Clinically staged - cT1-4 N0-2 M0 (local or locally advanced, resectable)
- •Eligible for multidisciplinary treatment as assessed by MDT
- •Able to provide informed consent (ICF) according to Good Clinical Practice and national/European regulations
排除标准
- •(Oligo)metastatic disease
- •Histologically or cytologically confirmed diagnosis other than squamous cell carcinoma or adenocarcinoma (eg. neuroendocrine carcinoma, lymphoma…)
- •Other active malignancies
- •Previous exposure to chemoradiation (prior to MDT)
- •Treatment plan after MDT: neoadjuvant chemotherapy with no radiation or chemoradiation with definitive intent (surgery is not planned)
研究组 & 干预措施
1. primary resection then follow-up
Scenario 1: primary resection then follow-up - Study-specific liquid biopsies will be collected in 98 patients, at the time of routine labs. Samples will be acquired before resection, at 6-8 weeks, 6 and 12 months after resection.
干预措施: Blood sample (Other)
2. chemoradiation followed by resection and follow-up
Scenario 2: chemoradiation followed by resection and follow-up - Study-specific liquid biopsies will be collected in 50 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks, 6 and 12 months after surgery. A subgroup of patients will undertake adjuvant immunotherapy and will constitute Group 3. Timing of sampling will be adjusted accordingly as per study flowcharts.
干预措施: Blood sample (Other)
3. chemoradiation followed by resection followed by adjuvant immunotherapy
chemoradiation followed by resection followed by adjuvant immunotherapy - Study-specific liquid biopsies will be collected in 100 patients. Samples will be acquired before the start of chemoradiation, before surgery, 6-8 weeks after surgery and during adjuvant immunotherapy every 3 months including a sample at the end of treatment.
干预措施: Blood sample (Other)
结局指标
主要结局
To correlate the presence of minimal residual disease after resection as assessed by ctDNA with disease recurrence.
时间窗: 12 months
To compare the two groups ctDNA positive and negative post-resection in terms of progression-free survival and overall survival (Kaplan-Meier time-to-event) and evaluate the performance of ctDNA to predict disease recurrence (Cox proportional hazards model).
To assess the potency of ctDNA MRD variant allele frequency to improve clinical staging at diagnosis of esophageal cancer.
时间窗: 12 months
To assess whether ctDNA concentration can significantly contribute to preoperative staging in esophageal cancer, to define a significant cut-off value of ctDNA concentration with optimal sensitivity and specificity and validate the results.
To observe the ctDNA MRD dynamics during adjuvant immunotherapy .
时间窗: 12 months
To describe the dynamics of ctDNA concentration (proportion of clearance of positive ctDNA) during standard of care adjuvant immunotherapy.
次要结局
未报告次要终点