Circulating Tumor DNA Methylation Guided Postoperative Follow-up Strategy for Non-metastatic Colorectal Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorFudan University
About this trial
Colorectal cancer (CRC) is one of the most common gastrointestinal tumors. According to the latest cancer report, the incidence and mortality rates of CRC are both ranked top 5 among malignant tumors worldwide and continue to rise. Patients who receive treatment in the early stage (stage I) have a 5-year survival rate of approximately 90%. However, for high-risk stage II and III colorectal cancer patients, the 5-year survival rate is only 40%-70%, and almost half of the patients experience postoperative recurrence and metastasis.
Circulating tumor DNA (ctDNA) is a small fraction of total cell-free DNA (cfDNA) in peripheral blood circulation, carrying tumor-specific genetic and epigenetic information. It can usually be detected in the serum or plasma of tumor patients in peripheral blood. Studies have shown that methylation detection of plasma ctDNA can be used for predicting the efficacy and prognosis of tumor postoperatively, as well as for dynamic monitoring.
Current methods for monitoring CRC recurrence include testing for carcinoembryonic antigen (CEA) in blood and periodic computed tomography (CT) scans. However, due to the low sensitivity of CEA and the radiation and cost limitations of CT examination, the disease status of postoperative CRC patients cannot be well-monitored.
ctDNA is a promising biomarker for monitoring the recurrence and metastasis of CRC. Research results have shown that ctDNA can be detected in nearly all subjects before surgery, and the changes in ctDNA levels are related to the extent of surgical resection. The detection of ctDNA after surgery generally indicates recurrence within one year. ctDNA may be a more reliable and sensitive indicator than the current standard biomarker CEA, providing a window for early intervention.
This multicenter, prospective, and randomized controlled cohort study uses a single-tube methylation-specific quantitative PCR (mqMSP) detection, which detects 10 different methylation markers and can quantitatively analyze plasma samples containing tumor DNA as low as 0.01%. This study will use the ctDNA methylation detection technology to conduct quantitative detection of ctDNA methylation in the plasma of enrolled patients, hoping to predict the recurrence and metastasis risk of patients at an earlier stage through ctDNA changes, and to explore the value of ctDNA detection in guiding postoperative follow-up for non-metastatic CRC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years old, regardless of gender;
Personal status (PS) score as over 80 or Eastern Cooperative Oncology Group (ECOG) score as 0 ~ 2;
Preoperative imaging examinations reveal no definite distant metastatic lesions, and postoperative pTNM staging confirms patients with stage I to III colorectal cancer;
Radical operation performed ;
Disqualifiers
Blood transfusion performed during operation or within 2 weeks before operation;
Incomplete baseline samples, including preoperative plasma samples;
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;
Trial design
Design model
Parallel
Treatments tested in this trial
ctDNA methylation dynamic monitoring
Diagnostic testctDNA methylation detection is performed within one month before surgery, within one month after surgery, and every three months after surgery, for a period of 2 years.
Treatment groups
584 Participants
are divided into 2 treatment groupsGroup A: ctDNA dynamic monitoring + routine postoperative follow-upExperimental treatment 1 intervention
Group B: Routine postoperative follow-upNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
Secondary curative-intent rate
This study primarily evaluates whether ctDNA-informed surveillance after surgery increases the proportion of patients with CRC recurrence who receive curative-intent or metastasis-directed therapy, compared to the standard follow-up protocol within 2 years of initial surgery.
Time frame
Up to 24 monthsSecondary outcomes
1
TTCR
To exam whether ctDNA-guided surveillance leads to a reduced time to clinical recurrence (TTCR) compared to standard surveillance.
Time frame
Up to 60 months2
DFS
To investigate ctDNA-based disease-free survival (ctDNA-DFS), CT-based disease-free survival (CT-DFS), and the difference between ctDNA-DFS and CT-DFS (△-DFS).
Time frame
Up to 60 months3
Sensitivity of postoperative ctDNA monitoring for detecting recurrence
To investigate sensitivity of postoperative ctDNA monitoring for detecting recurrence (Sensitivity=Number of ctDNA-positive patients confirmed with recurrence by imaging/Total number of patients confirmed with recurrence by imaging).
Time frame
Up to 60 months4
Specificity of postoperative ctDNA monitoring for detecting recurrence
To investigate specificity of postoperative ctDNA monitoring for detecting recurrence (Specificity= Number of ctDNA-negative patients confirmed without recurrence by imaging /Total number of patients confirmed without recurrence by imaging).
Time frame
Up to 60 monthsSponsors and contacts
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Source ClinicalTrials.gov