Clinical trial NCT06879886: MRD-Guided Surveillance in Resectable Stage IV Metastatic Colorectal Cancer (SURVEILLANCE-II)
Official title: MRD-Guided Surveillance in Resectable Stage IV Metastatic Colorectal Cancer (SURVEILLANCE-II)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Colorectal Cancer (CRC)
Colorectal Cancer Liver Metastases (CRLM)
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2025-03-17
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consists of patients diagnosed with resectable stage IV metastatic colorectal cancer (mCRC) who have not received prior systemic treatment. Participants will be recruited from multiple clinical centers and must meet specific eligibility criteria to ensure the study's validity.

Key Characteristics of the Study Population:

Diagnosis: Histologically confirmed colorectal adenocarcinoma (including adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma; excluding adenosquamous carcinoma).

Stage: Clinical stage IV disease, confirmed by preoperative imaging and clinical assessment as having resectable primary and metastatic lesions.

Treatment History: No prior chemotherapy, radiotherapy, targeted therapy, or other anti-cancer treatments.

Surgical Eligibility: Candidates must be eligible for curative-intent resection of both the primary tumor and metastatic lesions.

General Health Status: ECOG performance status 0-1, indicating

Brief summary: This study aims to explore the relationship between minimal residual disease (MRD) status and disease recurrence in patients with resectable stage IV metastatic colorectal cancer (mCRC). MRD refers to the presence of cancer cells that remain in the body after treatment but are undetectable by traditional imaging methods. The study will use a blood-based circulating tumor DNA (ctDNA) methylation test to assess its ability to predict cancer recurrence and survival outcomes.

Patients who are newly diagnosed with resectable stage IV mCRC and have not yet received any treatment will be enrolled. Blood samples will be collected at multiple time points, including before surgery, after surgery, and during follow-up visits over two years. The study will compare MRD status with recurrence-free survival (RFS), overall survival (OS), and the time it takes for MRD to detect recurrence compared to standard imaging methods.

The goal is to determine whether MRD monitoring can provide an early warning of cancer recurrence and help guide treatment decisions. This study may offer valuable insights into improving postoperative surveillance and personalized treatment strategies for metastatic colorectal cancer patients.

Detailed description: This is a multicenter, prospective, observational study designed to evaluate the effectiveness of ctDNA-based MRD monitoring in predicting disease recurrence and survival outcomes in patients with resectable stage IV metastatic colorectal cancer (mCRC). The study will enroll 181 patients who have not previously received chemotherapy, radiotherapy, or targeted therapy.

Key Objectives

Primary Objective:

To explore the correlation between MRD status and recurrence-free survival (RFS) in resectable stage IV mCRC patients.

Secondary Objectives:

To assess the relationship between MRD status and 1-year/2-year event-free survival (1yEFS, 2yEFS).

To evaluate the association between MRD status and 2-year recurrence-free survival (2yRFS).

To assess the impact of MRD status on overall survival (OS).

Exploratory Objective:

To determine the average time by which MRD detection precedes imaging-based detection of disease recurrence.

Study Design

Patients will undergo blood sampling at key time points:

Baseline (pre-treatment) Pre-surgery (0-7 days before surgery) Post-surgery (7±2 days after surgery) Follow-up visits at 1, 3, 6, 9, 12, 18, and 24 months post-surgery MRD status will be assessed using a ctDNA methylation-based PCR test, which provides a rapid, cost-effective alternative to traditional NGS-based methods.

Statistical Analysis Kaplan-Meier survival analysis will be used to estimate RFS, EFS, and OS. Cox proportional hazards models will assess whether MRD status serves as an independent prognostic factor for recurrence.

Multivariate analysis will adjust for clinical variables, including tumor burden and treatment history.

Ethical Considerations The study adheres to the principles of the Declaration of Helsinki and Chinese Good Clinical Practice (GCP) guidelines.

Informed consent will be obtained from all participants, and privacy and confidentiality will be strictly maintained.

Expected Outcomes This study aims to validate the clinical utility of ctDNA-based MRD monitoring in predicting recurrence and survival outcomes for resectable stage IV mCRC patients. If successful, MRD testing may offer a more effective tool for postoperative surveillance and treatment planning, allowing for earlier interventions and improved long-term outcomes.

Eligibility criteria: Inclusion Criteria:

1. Age 18-80 years old, male or female;
2. histologically confirmed primary foci of colorectal adenocarcinoma (i.e., adenoepithelial carcinoma, including adenocarcinoma, mucinous adenocarcinoma, imprinted cell carcinoma, and undifferentiated carcinoma; excluding adenosquamous carcinoma); (3) Preoperative stage IV and no surgical resection; (4) Not receiving chemotherapy, radiotherapy, targeted therapy or other anti-tumor therapy;

5) Surgical resection of primary/metastatic foci is possible; 6) ECOG score 0-1; 7) Subjects voluntarily enrolled in the study and signed the informed consent, good compliance, and actively cooperate with the regular clinical follow-up clinic back in the hospital.

Exclusion Criteria:

1. Previous other malignant tumors (including non-adenocarcinoma colorectal cancer);
2. Pregnant and lactating women;
3. Patients with other concurrent illnesses that, in the judgment of the investigator, may interfere with follow-up and short-term survival;
4. The subject has other factors that may cause this study to be forced to be terminated halfway, such as other serious illnesses (including psychiatric illnesses) that require comorbid treatment, serious laboratory test abnormalities, accompanied by family or social factors that would affect the safety of the subject, or the collection of data and samples.

Primary outcomes:
measure: Exploring the correlation between MRD status and rate of disease recurrence (RFS) in people with stage IV metastatic resectable colorectal cancer
timeFrame: From surgery to disease recurrence or up to 24 months
Secondary outcomes:
measure: Correlation of MRD status with 1-year event-free survival (1yEFS)
timeFrame: From surgery to 12 months
measure: Correlation of MRD status with 2-year event-free survival (2yEFS)
timeFrame: From surgery to 24 months
measure: Correlation of MRD status with 2-year recurrence-free survival (2yRFS)
timeFrame: From surgery to 24 months
measure: Correlation of MRD status with overall survival (OS)
timeFrame: From surgery to death or up to 24 months
Other outcomes:
measure: MRD detects disease recurrence earlier than imaging (CT) average advance time
timeFrame: From surgery to disease recurrence, assessed up to 24 months
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