Using ctDNA Methylation to Monitor Metastatic Colorectal Cancer Treatment (PROMET)

ctDNA Methylation for Efficacy Assessment and Prognostic Prediction in Advanced Colorectal Cancer Treated With Radiotherapy Combined With or Without PD-1 Inhibitor: A Prospective Cohort Study (PROMET)

Multi-center observational clinical study to evaluate the application value of ctDNA methylation monitoring in efficacy assessment and relapse prediction in patients diagnosed with recurrence or metastatic colorectal cancer receiving radiotherapy plus SOC with or without PD-1.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer ctDNA Surveillance
• Intervention / Treatment: Diagnostic test: Plasma ctDNA methylation profiling

Detailed Description

This study will enroll patients with histologically confirmed, recurrent or metastatic colorectal cancer who are eligible to receive radiotherapy in combination with standard-of-care chemotherapy, with or without PD-1 inhibitors. The study will employ ctDNA methylation detection technology to quantitatively assess ctDNA methylation levels in patient plasma samples. Blood samples will be collected at baseline and at multiple predefined timepoints during treatment. In addition, participants will undergo standard imaging surveillance (CT/MRI) every three months. The study aims to correlate ctDNA dynamics with therapeutic response, time to recurrence, and survival outcomes. Ultimately, it seeks to evaluate the potential of ctDNA monitoring for predicting treatment efficacy and prognosis, and to explore its utility in guiding clinical management for metastatic colorectal cancer.

• Study Type: Observational
• Enrollment (Estimated): 497

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhen Zhang, MD, PhD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Histologically confirmed, recurrent or metastatic colorectal cancer who are eligible to receive radiotherapy in combination with standard-of-care chemotherapy, with or without PD-1 inhibitors.

Description

Inclusion Criteria:

1. Age ≥ 18 years old, regardless of gender;
2. Histologically confirmed, recurrent or metastatic colorectal cancer;
3. Eligible to receive radiotherapy in combination with standard-of-care chemotherapy, with or without PD-1 inhibitors.
4. With expected survival of more than 6 months;
5. 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.

Exclusion Criteria:

1. Blood transfusion performed during operation or within 2 weeks before operation;
2. Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;
3. Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;
4. Primary brain tumor or central nerve metastasis is not under control, with obvious intracranial hypertension or neuropsychiatric symptoms;
5. 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;
6. Significant impairment of important organ function;
7. Other conditions in which the investigator believes that the patient should not participate in this trial.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Experimental group; Newly diagnosed, histologically confirmed, recurrent or metastatic colorectal cancer, amenable to receive radiotherapy in combination with standard-of-care chemotherapy, with or without PD-1 inhibitors. Patients will receive dynamic monitoring of ctDNA + routine follow-up: ctDNA detection is performed at baseline, multiple predefined timepoints during treatment and follow-up for a period of 2 years. At the same time, participants will undergo routine imaging surveillance (CT/MRI) every three months.

Diagnostic test: Plasma ctDNA methylation profiling; Plasma ctDNA methylation profiling was performed using an optimized single-tube multiplex mqMSP assay

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	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).	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	To exam whether 3- and 5-year overall survival (OS) with ctDNA-guided surveillance is comparable to that achieved with standard CT-based monitoring.	up to 5 year
Patient-reported outcomes (quality of life)	To assess patient-reported outcomes-quality of life (EORTC QLQ-C30)-in those receiving ctDNA-guided versus standard surveillance.	up to 5 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2025
• Primary Completion (Estimated): October 10, 2028
• Study Completion (Estimated): October 10, 2030

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 4, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Radiotherapy; ctDNA methylation; Metastatic Colorectal Cancer(mCRC)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2025-364-4513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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