MRD-guided Deferred Adjuvant Therapy in Resectable Early-stage Colon Cancer

NCT06204484 | Recruiting

• 1 other identifier: MIRROR
• Study Type: interventional
• Target: 349
• Locations: 1 country
• Sites: 1

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:

1. 1.Whether patients with MRD negative status could benefit from deferred adjuvant therapy.
2. 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.

Conditions

Colorectal Cancer

Keywords

circulating tumor DNA; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

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

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

  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.

Secondary Outcomes (3)

• 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.

• OS time in MRD+ groups

  From the date of randomization until the date of death from any cause, assessed up to 5 years.

Other Outcomes (3)

• Dynamic change of MRD status and ctDNA concentration during follow-up

  Assessed up to 5 years.

• Association between dynamic change of MRD status and ctDNA concentration and disease-free survival

  Assessed up to 5 years.

• Performance of landmark MRD status and longitudinal MRD status in prediction of recurrence.

  Assessed up to 5 years.

Study Arms (4)

MRD-negative standard adjuvant therapy

ACTIVE COMPARATOR

In MRD-negative standard therapy groups, patients will receive 3-month capecitabine and oxaliplatin (CAPEOX) therapy.

Other: CAPEOX adjuvant therapy

MRD-negative deferred adjuvant therapy

EXPERIMENTAL

In MRD- deferred adjuvant therapy group, patients won't get the standard CAPEOX adjuvant therapy at first. When MRD negative status turns to positive status, the 3-month CAPEOX therapy will be arranged.

Other: deferred CAPEOX adjuvant therapy

MRD-positive standard adjuvant therapy

ACTIVE COMPARATOR

In MRD-positive standard therapy groups, patients will receive 3-month CAPEOX therapy, regardless of the MRD status.

Other: CAPEOX adjuvant therapy

MRD-positive intensive adjuvant therapy

EXPERIMENTAL

In the MRD+ intensive standard therapy group, which represents a high risk of recurrence, patients will receive 3-month modified folinic acid, fluorouracil, oxaliplatin and irinotecan (mFOLFOXIRI) intensive therapy, instead of the CAPEOX standard adjuvant therapy.

Other: mFOLFOXIRI intensive adjuvant therapy

Interventions

CAPEOX adjuvant therapy OTHER

In MRD-/+ standard therapy groups, patients will receive 3-month CAPEOX therapy, regardless of the MRD status.

MRD-negative standard adjuvant therapy; MRD-positive standard adjuvant therapy

deferred CAPEOX adjuvant therapy OTHER

In MRD-negative deferred adjuvant therapy group, patients won't get the standard CAPEOX adjuvant therapy at first. When MRD negative status turns to positive status, the 3-month CAPEOX therapy will be arranged.

MRD-negative deferred adjuvant therapy

mFOLFOXIRI intensive adjuvant therapy OTHER

In the MRD+ intensive standard therapy group, which represents a high risk of recurrence, patients will receive 3-month mFOLFOXIRI intensive therapy, instead of the CAPEOX standard adjuvant therapy.

MRD-positive intensive adjuvant therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Patients with multiple primary colorectal cancer;
• Received other parts of open surgery rather than the colon within 14 days prior to the patient's enrollment;
• Cannot provide surgical tissues for customized personalized MRD testing or fail to customize personalized MRD testing panels.
• Cannot provide pre-operative blood, POD 3-7 blood, and POD 21-30 for MRD testing.
• Suffer from other serious diseases that may affect the follow-up and short-term survival according to the judgment of the investigators;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Guangzhou Burning Rock Dx Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Gong Chen, PhD

CONTACT

+86 20 87343584; chengong@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 28, 2023
• First Posted: January 12, 2024
• Study Start: July 26, 2023
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: January 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)