Circulating Tumor DNA Methylation Guiding Postoperative Adjuvant Chemotherapy in Stage III Colorectal Cancer (cmPAT)

Circulating Tumor DNA Methylation Guiding Postoperative Adjuvant Chemotherapy in Stage III Colorectal Cancer: a Multicenter, Randomized Controlled Trial

The goal of this randomized controlled trial is to investigate whether ctDNA methylation is a more precise indicator to guide postoperative adjuvant chemotherapy in stage Ill colorectal cancer. The main questions it aims to answer are:

1. Whether ctDNA methylation-guided escalation strategy is superior to standard treatment for stage III high-risk CRC patients.
2. Whether ctDNA methylation-guided de-escalation strategy is non-inferior to standard treatment for stage III low-risk CRC patients.

325 cases were included in the high-risk cohort (T4 and/or N2) and 665 cases were included in the low-risk cohort (T1-T3, N1). Then patients in each cohort were randomly assigned to ctDNA-guided treatment (ctDNA-guided group) and standard treatment (standard treatment group) in a ratio of 2:1. The standard treatment group and ctDNA-negative group in the high-risk cohort were treated with XELOX regimen for 6 months, and the ctDNA-positive group in the high-risk cohort was treated with cmFOLFOXIRI regimen for 6 months. The standard treatment group and the ctDNA-positive group in the low-risk cohort were treated with XELOX regimen for 3 months, while the ctDNA-negative group in the low-risk cohort did not receive adjuvant chemotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Diagnostic test: ctDNA methylation; Diagnostic test: standard treatment

• Study Type: Interventional
• Enrollment (Estimated): 990
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bingjun Bai, Dr; Phone Number: +8613858816897; Email: echobai@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310012
      • Sir Run Run Shao hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18 years old ≤ age < 75 years old.
2. Stage III (T1-4, N1-2, M0) colorectal cancer patients.
3. Patients who can undergo R0 resection.
4. ECOG score 0 ~ 2.
5. Expected survival ≥ 6 months.
6. No history of other malignant tumors.
7. Voluntarily participate in this study and sign the informed consent. If the subject does not have the ability to read the informed consent (e.g., illiterate subjects), a witness must witness the informed process and sign the informed consent.

Exclusion Criteria:

1. Patients who have received neoadjuvant chemotherapy.
2. Known high clinical risk of adjuvant chemotherapy.
3. Patients with clear contraindications to adjuvant chemotherapy (i.e. due to physical condition, comorbidities, active second cancer, or age).
4. Patients who are unable to undergo subsequent chemotherapy due to other reasons (travel distance, compliance).
5. Vulnerable groups, including people with mental illness, people with cognitive impairment, critically ill patients, minors, pregnant women, etc.
6. There are any other circumstances that the researcher deems unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ctDNA-guided group; ctDNA-negative group in the high-risk cohort were treated with XELOX regimen for 6 months; ctDNA-positive group in the high-risk cohort was treated with cmFOLFOXIRI regimen for 6 months; ctDNA-positive group in the low-risk cohort were treated with XELOX regimen for 3 months; ctDNA-negative group in the low-risk cohort did not receive adjuvant chemotherapy.	Diagnostic test: ctDNA methylation; A blood-based circulating tumor DNA methylation assay that uses 6 different methylation markers, SEPT9 region1, SEPT9 region2, BCAT1, IKZF1, BCAN and VAV3.
Active Comparator: standard treatment group; The standard treatment group in the high-risk cohort were treated with XELOX regimen for 6 months, and in the low-risk cohort were treated with XELOX regimen for 3 months.	Diagnostic test: standard treatment; This group was treated according to standard procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence-free survival at 3 years	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival at 5 years	5 years
ctDNA clearance rate in ctDNA-positive patients treated with adjuvant chemotherapy	6 months
The proportion of patients in the low-risk cohort who did not receive adjuvant chemotherapy	6 months

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital
• Investigators: Principal Investigator: Zhangfa Song, Dr, Sir Run Run Shaw Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Estimated): December 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer; adjuvant chemotherapy; ctDNA methylation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: SRRS-cmPAT; SRRS2023-0704 (Registry Identifier: Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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