The Effectiveness of Deferred Adjuvant Therapy Guided by Dynamic Monitoring Minimal Residue Disease in Resectable High-risk Stage II and Low-risk Stage III Colon Cancer: an Open-label, Multicenter, Phase II Clinical Study

Sun Yat-sen University1 site in 1 country349 target enrollmentJuly 26, 2023

ConditionsColorectal Cancer

Overview

Phase: N/A
Intervention: Not specified
Conditions: Colorectal Cancer
Sponsor: Sun Yat-sen University
Enrollment: 349
Locations: 1
Primary Endpoint: Relapse-free survival (RFS) time in MRD-negative groups
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The aim of this clinical trial is to test whether minimal residual disease (MRD) status detected by circulating tumor DNA (ctDNA) could be used to guide precision therapy of post-surgery in colon cancer. The colon cancers are intended for resectable colon cancer of high-risk stage II and low-risk stage III status. The main questions it aims to answer are:

Whether patients with MRD negative status could benefit from deferred adjuvant therapy.
Whether patients with MRD positive status need intensive adjuvant therapy. The qualified participants will go through two different randomized groups according to the post-surgery 1-month MRD status. In MRD negative groups, participants will be divided into standard adjuvant therapy groups and deferred adjuvant therapy groups at 1:2 ratios. In MRD positive groups, participants will be divided into standard adjuvant therapy groups and intensive adjuvant therapy groups at 1:2 ratios. All the patients will receive MRD detection every 3 months and radiological evaluation every 6 months up to 3 years, and survival follow-up up to 5 years.

Registry

clinicaltrials.gov

Start Date

July 26, 2023

End Date

July 31, 2028

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Sun Yat-sen University

Responsible Party

Principal Investigator

Gong Chen

Professor

Sun Yat-sen University

Eligibility Criteria

Inclusion Criteria

•Participants must fit all of the following inclusion criteria to be enrolled in this study:
•Over 18 years old (including 18 years old) and under 70 years old (including 70 years old) when signing the informed consent form;
•The Eastern Cooperative Oncology Group (ECOG) physical status scores are 0-1 and do not deteriorate within 2 weeks before enrollment. The expected survival time is no less than 12 weeks;
•Histological or cytological confirmed stage II high-risk and stage III low-risk none high microsatellite instability (MSI-H) colon adenocarcinoma according to the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) primary tumor, regional nodes, metastasis (TNM) stage (8th edition). High-risk factors for stage II patients include: T4, poorly differentiated histology (high-grade, excluding MSI-H status), vascular invasion, neural invasion, intestinal obstruction or tumor site perforation pre-operation, positive or unknown margins, insufficient margin distance and examined lymph nodes less than 12; Stage III low-risk patients include patients with T1-3 N1 (excluding T4 or N2).
•No evidence of distant metastasis (distant organ and/or distant lymph node metastasis) confirmed by comprehensive examination;
•The distal end of the tumor is ≥12cm from the anal edge evaluated by pre-operative endoscopy. If the endoscopy is absent before surgery, the distance could be evaluated by radiology or during the surgery;
•Patients who have not received neoadjuvant therapy and can achieve R0 radical resection;
•Sufficient surgical fresh tissue samples for customized personalized MRD testing panels detected by whole exome sequencing (WES); available for preoperative blood, post-operative day (POD) 3-7 blood, and POD 21-30 blood samples for MRD testing;
•Females of the childbearing period should take appropriate contraceptive measures and should not breastfeed from the screening stage to 3 months post-treatment. Before starting treatment, a negative pregnancy test, or one of the following criteria should be confirmed for no risk of pregnancy:
•Post-menopause, defined as age greater than 50 years and amenorrhea for at least 12 months after cessation of all exogenous hormone replacement therapy.

Exclusion Criteria

•Participants who meet any of the following criteria are not eligible for this study:
•Received any of the following treatments:
•Received neoadjuvant therapy in the past;
•Previously received any systemic chemotherapy or immunotherapy for colon cancer;
•Previously received any radiotherapy for colon cancer;
•Undergone colon cancer surgery in the past;
•Previously or concomitantly diagnosed of other malignant tumors (except for adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer);
•Patients with other histological types rather than adenocarcinoma (such as neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.);
•MSI-H/deficient mismatch repair (dMMR) patients;
•Pathological, clinical, or radiologic evidence of metastatic lesions, including isolated, distant, or discontinuous intra-abdominal metastases;

Outcomes

Primary Outcomes

Relapse-free survival (RFS) time in MRD-negative groups

Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

To evaluate the 3-year RFS time in MRD guided deferred adjuvant therapy groups

Secondary Outcomes

OS time in MRD+ groups(From the date of randomization until the date of death from any cause, assessed up to 5 years.)
Overall survival (OS) time in MRD-negative groups(From the date of randomization until the date of death from any cause, assessed up to 5 years.)
RFS time in MRD-positive groups(From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.)