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
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: 1. Whether patients with MRD negative status could benefit from deferred adjuvant therapy. 2. 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.
• 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.
‣ Women younger than 50 years who have been amenorrhea for 12 months or more after cessation of all exogenous hormone therapy and whose luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within laboratory postmenopausal reference values can also be considered as post-menopausal.
‣ Have undergone irreversible sterilization surgery, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, except bilateral tubal ligation.
• Male participants should use barrier contraception (i.e., condoms) from the screening stage to 3 months post-treatment;
⁃ The participants volunteer to join in the study and signed the informed consent in writing;
⁃ Patients who are suitable for CAPEOX and mFOLFOXIRI adjuvant therapy.