Evaluation of Circulating Tumor DNA Guided Surveillance Strategy of Stage III Colorectal Cancer: an Open, Prospective, Randomized Controlled Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 316
- 试验地点
- 1
- 主要终点
- Accuracy of postoperative ctDNA in monitoring recurrence and metastasis
研究概览
简要总结
For patients with stage III colon cancers, radical resection of primary tumor followed by adjuvant chemotherapy is currently the standard treatment. Adjuvant chemotherapy with 5-fluorouracil and oxaliplatin based regimen has been proved effective to improve recurrence-free survival and overall survival. Approximately half of patients with stage III colon cancers can be cured by surgery alone, while a substantial number of patients still experience recurrence, even with standard adjuvant chemotherapy. In recent years, circulating tumor DNA (ctDNA) has been detected in the cell-free component of peripheral blood samples in advanced colorectal cancers and many other solid tumors. Several previous studies have suggested that in patients with stage I-III colorectal cancer, postoperative ctDNA was an valuable biomarker to predict minimal residual disease (MRD) after radical resection, thus redefining patients risk outcome groups and guiding postoperative treatment. In addition, recent studies based on serial postoperative ctDNA detection showed that serial ctDNA analyses revealed disease recurrence up to 5-16.5 months ahead of radiological imaging. Here, based on the role of ctDNA in predicting MRD, we conducted an open, prospective, randomized controlled phase II cohort study to explore if ctDNA can as a biomarker to guide personalized surveillance strategy after surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
盲法说明
Postoperative adjuvant therapy (chemotherapy and radiotherapy) and specific implementation scheme shall be determined by the clinical physician blinded to ctDNA status and randomized group. Other parts are open-label.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 and ≤80 years old, regardless of gender;
- •Personal status (PS) score as over 80 or Eastern Cooperative Oncology Group (ECOG) score as 0 ~ 2;
- •Pathologically confirmed as stage III colorectal cancer;
- •Radical operation performed ;
- •With expected survival of more than 12 months;
- •The subjects (or their legal representative / Guardian) must sign the informed consent form, indicating that they understand the purpose of the study, understand the necessary procedures of the study, and are willing to participate in the study.
排除标准
- •Neoadjuvant therapy performed before operation;
- •Blood transfusion performed during operation or within 2 weeks before operation;
- •Incomplete baseline samples, including preoperative plasma samples, surgical tumor tissue samples and plasma samples 3-7 days after operation;
- •Two consecutive test points missing or three plasma samples missing in total before a positive ctDNA time point
- •Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;
- •Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;
- •Primary brain tumor or central nerve metastasis is not under control, with obvious intracranial hypertension or neuropsychiatric symptoms;
- •Patients with the following serious or uncontrollable diseases: severe heart disease, the condition is still unstable after treatment, including myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment; definite neuropathy or psychosis, including dementia or seizures; severe or uncontrolled infection; active disseminated intravascular coagulation and obvious bleeding tendency;
- •Significant impairment of important organ function;
- •Other conditions in which the investigator believes that the patient should not participate in this trial.
结局指标
主要结局
Accuracy of postoperative ctDNA in monitoring recurrence and metastasis
时间窗: Up to 60 months.
True positive+True negative/sample size
Secondary resection rate
时间窗: Up to 60 months.
The rate of R0 resection for recurrence or metastasis after surgery of the primary
Specificity of postoperative ctDNA in monitoring recurrence and metastasis
时间窗: Up to 60 months.
Number of patients with ctDNA negative and no recurrence and metastasis confirmed by imaging / number of patients with no recurrence and metastasis confirmed by imaging
Sensitivity of postoperative ctDNA in monitoring recurrence and metastasis
时间窗: Up to 60 months.
Number of patients with ctDNA positive and imaging confirmed recurrence or metastasis / number of all imaging confirmed recurrence or metastasis
次要结局
- ctDNA-disease free survival (DFS)(Under ctDNA monitoring, from date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.)
- overall survival (OS)(From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months.)
- ctDNA clearance rate(Up to 60 months.)
- CT-DFS(Under imaging monitoring, from date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60 months.)
- △DFS(Up to 60 months.)
研究者
Junjie Peng
Department of Colorectal Surgery，Fudan University Shanghai Cancer Center
Fudan University