A Prospective Multicentre Clinical Study of Dynamic Monitoring of Plasma ctDNA Methylation Markers to Predict Recurrence of Colorectal Cancer After Complete Resection of Peritoneal Metastases

The goal of this clinical trial is to explore the predictive effect of postoperative plasma ctDNA methylation status on postoperative recurrence free survival (RFS) of colorectal cancer patients with peritoneal metastasis after R0/R1 resection. The main questions it aims to answer are:

Preoperative and postoperative plasma ctDNA methylation detection (ColonAiQ) was performed in patients with peritoneal metastasis from colorectal cancer who underwent R0/R1 resection. Clinical information of patients was collected to explore the predictive effect of postoperative plasma ctDNA methylation status on postoperative recurrence free survival (RFS) of colorectal cancer patients with peritoneal metastasis.

Participants will:

The patients were followed up according to the normal review procedure of the hospital and the NCCN guidelines until at least 24 months after surgery. The review content included CT/MRI imaging evaluation and blood CEA (every 3 months). Whole-blood samples were obtained for timely plasma separation and ctDNA extraction at 1 month after surgery (before the start of postoperative chemotherapy) and every 3 months through 24 months after surgery. One blood sample was obtained when tumor recurrence was first detected on imaging.

Detection of methylation in tissue and plasma samples

1. GutSeer methylation NGS was performed on peritoneal metastatic cancer tissues and paired normal peritoneal tissues.
2. ctDNA GutSeer methylation NGS was performed on plasma samples before surgery, 1 month after surgery, 24 months after surgery, and when tumor recurrence was first detected by imaging examination.
3. ctDNA methylation PCR (ColonAiQ) was performed on plasma samples before surgery, 1 month after surgery, every 3 months to 24 months after surgery, and when tumor recurrence was first detected by imaging examination.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Peritoneal Metastases
• Intervention / Treatment: Other: As an observational study, we did not intervene

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Guoxiang Cai, MD, PhD; Phone Number: +86-18819431363; Email: hanlingyu_ann@sina.cn
• Study Contact Backup: Name: Lingyu Han, MD, PhD; Phone Number: +86-19521330776; Email: lingyuhan24@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Weijing Zhang; Phone Number: 88503 021-64175590

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with peritoneal metastasis from colorectal cancer whose preoperative imaging PCI score was ≤20 and could be evaluated for R0/R1 resection were screened for enrollment. Preoperative plasma samples and tumor tissue samples were collected for ctDNA multigene methylation markers detection. Patients who achieved R0/R1 resection of peritoneal carcinomatosis were enrolled in this clinical study.

Description

Inclusion Criteria:

-1. No gender limit, age greater than 18 years old; 2, ECOG score ≤1; 3. Life expectancy ≥2 years; 4. Colorectal adenocarcinoma/mucinous adenocarcinoma/signet ring cell carcinoma confirmed by histopathology; 5, preoperative PCI score ≤20, peritoneal tumor cytoreductive surgery (CRS), surgery to achieve R0/1 resection; 6. Be able to understand the situation of this study and sign the informed consent.

7. The primary colorectal cancer has undergone R0 resection, and there is no extraperitoneal metastasis (except ovary).

Exclusion Criteria:

• 1. Combined with primary malignant tumors of other organs (current or within the past 5 years) (excluding patients with skin basal cell carcinoma and cervical carcinoma in situ undergoing radical treatment); 2. Severe mental illness or drug abuse; 3, severe heart, lung, vascular disease can not tolerate surgery; 4. Pregnant or lactating women.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
POM1 positive; Patients whose 1-month-postoperative plasma ctDNA methylation status is positive	Other: As an observational study, we did not intervene; Interventions
POM1 negative; Patients whose 1-month-postoperative plasma ctDNA methylation status is negative	Other: As an observational study, we did not intervene; Interventions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predictive value of ColonAiQ postoperative recurrence free survival (RFS)	explore the predictive effect of postoperative plasma ctDNA methylation status on postoperative recurrence free survival (RFS) of colorectal cancer patients with peritoneal metastasis.	2023.10-2027.10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predictive value of GutSeer for RFS	Preoperative and postoperative plasma ctDNA polygene methylation test (GutSeer) was performed in patients with peritoneal metastasis from colorectal cancer who underwent R0/R1 resection, and the clinical information of patients' recurrence-free survival (RFS) was collected to explore the predictive effect of postoperative plasma ctDNA methylation status on postoperative RFS of colorectal cancer peritoneal metastasis.	2023.10-2027.10
predictive value of ctDNA for dynamic monitoring	To explore the predictive value of plasma ctDNA methylation status before surgery, after postoperative adjuvant chemotherapy, and regularly monitored after surgery for recurrence and metastasis of colorectal cancer patients with peritoneal metastasis	2023.10-2027.10
difference of predictive value of ColonAiQ and GutSeer	Compare the prognostic value of GutSeer and ColonAiQ and CEA at 1 month after surgery;	2023.10-2027.10
the advance time of dynamic detection of plasma ctDNA methylation compared with imaging monitoring	To explore the advance time of dynamic detection of plasma ctDNA methylation compared with imaging monitoring in monitoring recurrence after complete resection of peritoneal metastasis from colorectal cancer	2023.10-2027.10

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Sixth Affiliated Hospital, Sun Yat-sen University
• Investigators: Principal Investigator: Guoxiang Cai, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Recurrence; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: CRIP-ctDNA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The results of clinical trials will be published in the form of a paper, but content involving patient personal information or sensitive information will be kept confidential as required by the Ethics Committee

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No