Postoperative Circulating Tumor DNA Monitoring in Stage I-III Driver-Mutant Colon Adenocarcinoma (ADX-DRIVER-CRC)

August 29, 2026 updated by: Zhao Ren, Ruijin Hospital

Multicenter Prospective Cohort Study of Molecular Residual Disease (MRD) in Stage I-III Surgically Resectable Colon Adenocarcinoma Harboring Oncogenic Driver Mutations

This multicenter prospective observational cohort study will enroll 392 patients with stage I-III colon adenocarcinoma who undergo curative resection and whose tumors harbor at least one prespecified oncogenic driver mutation (KRAS, NRAS, BRAF, or PIK3CA). Serial plasma circulating tumor DNA (ctDNA) testing for molecular residual disease (MRD) will be performed with a standardized 10-gene next-generation sequencing (NGS) panel at predefined time points during 3 years of postoperative follow-up. The primary objective is to evaluate the association between postoperative ctDNA-based MRD status and recurrence-free survival (RFS). Secondary objectives include evaluating overall survival (OS), the interval between first MRD detection and radiologically confirmed recurrence, and the association between longitudinal MRD changes and outcomes following adjuvant chemotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background Colorectal cancer (CRC) ranks the 3rd most common malignancy worldwide and the 2nd leading cause of cancer death. In China, CRC incidence and mortality keep rapidly rising, with ~517,000 new cases and ~240,000 deaths annually. Radical resection is the curative standard for stage I-III CRC, yet postoperative recurrence reaches 20%-40% even after microscopically margin-negative (R0) resection. Traditional tumor-node-metastasis (TNM) staging and clinicopathological features fail to precisely stratify recurrence risk within the same stage, lacking capacity for early, real-time recurrence surveillance. Oncogenic driver mutations (KRAS, NRAS, BRAF, PIK3CA) dominate colorectal tumorigenesis and correlate with higher recurrence risk and worse prognosis, but static mutation status cannot reflect dynamic postoperative residual tumor burden. Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) enables non-invasive early detection of microscopic residual tumor, predicting recurrence months prior to radiological abnormalities, with strong prognostic value validated by multiple landmark trials. However, nearly all existing MRD cohorts lack stratification by driver mutation status; large-scale prospective multicenter data focusing exclusively on driver-mutant stage I-III colon adenocarcinoma are absent globally. This study fills the clinical gap by combining driver genotyping and longitudinal ctDNA-based MRD surveillance.

Scientific Hypothesis In patients with driver-mutant stage I-III resectable colon adenocarcinoma, postoperative ctDNA-based MRD status acts as an independent prognostic biomarker for recurrence regardless of conventional clinicopathological factors. Dynamic serial MRD shifts can alert tumor relapse earlier than routine contrast-enhanced computed tomography (CT), and different driver mutation subtypes demonstrate heterogeneous MRD detectability and predictive efficacy. Persistent MRD positivity predicts high recurrence risk, while sustained MRD negativity indicates excellent prognosis and potential de-escalation of adjuvant chemotherapy.

Study Design & Procedures A total of 10 tertiary hospitals with colorectal surgery and molecular pathology capacity will consecutively enroll eligible patients within 1 year. All participants receive standardized perioperative and follow-up care per clinical guidelines without study-mandated intervention modification. Serial peripheral blood samples (20 mL per draw) are collected at fixed time points: pre-operation (T0, baseline), postoperative day 7±2 (T1), 1 month post-surgery before adjuvant chemotherapy (T2), every 3 months up to 12 months (T3-T6), every 6 months at 18/24 months (T7-T8), and 36 months post-operation (T9). ctDNA-based MRD testing is performed centrally by Amoy Diagnostics using a fixed 10-gene next-generation sequencing (NGS) panel covering all core CRC driver mutations, sequencing depth ≥100,000×. MRD positivity is defined as detection of any tumor-derived driver mutation in plasma at any postoperative time point. All patients receive standardized 3-year follow-up: physical exam + tumor markers every 3 months in year 1; every 6 months in year 2; annual follow-up in year 3. Contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis is conducted every 6 months, colonoscopy at 12, 24 and 36 months postoperatively. All recurrence events are adjudicated by an blinded independent central review (BICR).

Statistical Plan Primary analysis uses Kaplan-Meier curves and log-rank test to compare RFS between MRD-positive and MRD-negative groups; multivariate Cox proportional hazards regression adjusts for age, sex, TNM stage, differentiation grade, adjuvant chemotherapy regimen and driver mutation subtype to confirm MRD as independent prognostic factor. Secondary endpoints including OS, 1- and 2-year RFS rates, median lead time of MRD ahead of radiological recurrence are analyzed via survival statistics. All statistical tests are two-sided with α=0.05, analyzed using R 4.3.0 and SPSS software. Sample size calculation accounts for 20% dropout rate, targeting total enrollment of 392 patients to ensure statistical power of 0.95 for primary endpoint analysis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
392

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 201801
        • Recruiting
        • Ruijin Hospital North
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients will be selected from consecutive adults evaluated for curative-intent surgery for pathologically confirmed stage I-III colon adenocarcinoma at 10 participating tertiary hospitals in China with colorectal surgery and molecular pathology capabilities. The study cohort will include eligible patients aged 18-75 years whose tumor tissue harbors at least one prespecified oncogenic driver mutation and who consent to serial postoperative blood collection and 3 years of follow-up.

Description

Inclusion Criteria:

  1. Age 18-75 years, regardless of sex
  2. Pathologically confirmed colon adenocarcinoma, clinical stage I-III without preoperative endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR)
  3. Planned curative surgical resection, no prior anti-tumor therapy (chemotherapy, radiotherapy, targeted therapy) before surgery
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  5. Tumor tissue positive for at least one driver mutation among KRAS, NRAS, BRAF, PIK3CA
  6. Voluntary participation with signed written informed consent, good compliance with scheduled follow-up and blood collection.

Exclusion Criteria:

  1. Received neoadjuvant chemotherapy, radiotherapy or targeted therapy before surgery
  2. History of other malignant tumors (excluding non-adenomatous colorectal neoplasms)
  3. Pregnant or breastfeeding women
  4. Severe concurrent systemic diseases that interfere with long-term follow-up or short-term survival (uncontrolled severe infection, organ failure, mental disorders, or other serious conditions)
  5. Abnormal laboratory values or social/family factors judged by investigator to impede sample collection and follow-up
  6. Simultaneous participation in other interventional clinical trials with mandatory assigned postoperative treatment regimen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Driver-mutant Stage I-III Resectable Colon Adenocarcinoma Cohort
Patients pathologically diagnosed with stage I-III colon adenocarcinoma, curatively resected, carrying ≥1 oncogenic driver mutation (KRAS/NRAS/BRAF/PIK3CA), aged 18-75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, without prior neoadjuvant therapy or other synchronous malignancy. All patients receive standard clinical surveillance plus serial blood draws for ctDNA-based MRD testing as observational biomarker testing only; no experimental treatment is assigned by the study protocol.
Other: Longitudinal ctDNA-MRD NGS testing at scheduled postoperative time points
biomarker test only

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Correlation between postoperative ctDNA-MRD status and Recurrence-Free Survival (RFS)
Time Frame: 3 years post curative resection
RFS is defined as time from curative surgery to radiology/pathology-confirmed recurrence/metastasis, all-cause death, or last follow-up (whichever occurs first). Evaluate statistical association between MRD positive/negative status and RFS via survival analysis.
3 years post curative resection

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation between ctDNA-MRD status and Overall Survival (OS)
Time Frame: 3 years post curative resection
OS defined as time from enrollment to all-cause death; compare OS between MRD-positive and MRD-negative subgroups
3 years post curative resection
Median lead time of MRD positivity prior to radiologically confirmed tumor recurrence
Time Frame: Up to 3 years postoperative follow-up
Calculate average interval between first detectable ctDNA-MRD and CT-verified disease relapse to quantify early warning advantage of MRD surveillance
Up to 3 years postoperative follow-up
Association between dynamic ctDNA-MRD changes and adjuvant chemotherapy efficacy
Time Frame: 3 years post curative resection
Analyze clinical outcome across MRD trajectory subgroups: sustained negative, intermittent positive, sustained positive, seroconversion from negative to positive
3 years post curative resection

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
MRD positive detection rate stratified by distinct oncogenic driver mutation subtypes
Time Frame: All serial blood testing time points within 3-year follow-up
Compare MRD detectability among driver gene mutant subgroups
All serial blood testing time points within 3-year follow-up
Prognostic predictive performance of ctDNA-MRD across different driver mutation subtypes
Time Frame: 3 years post curative resection
Evaluate heterogeneity of MRD's hazard ratio for recurrence among separate driver mutant cohorts
3 years post curative resection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ruijin Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The First Hospital of Jilin University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 14, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 23, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 31, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ADX-DRIVER-CRC-V1.0-20260518

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Access Criteria

Requestors must provide a methodologically sound research proposal, and data access will be granted via secure de-identified dataset transfer after signed data use agreement. Supporting documents including full protocol, statistical analysis plan, informed consent template, and de-identified clinical dataset will be accessible for qualified researchers for secondary biomarker validation analyses. No identifying personal information will be shared under any circumstance.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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