Postoperative Circulating Tumor DNA Monitoring in Stage I-III Driver-Mutant Colon Adenocarcinoma

NCT07795528 | Recruiting

• 1 other identifier: ADX-DRIVER-CRC-V1.0-20260518
• Study Type: observational
• Target: 392
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colon Adenocarcinoma; Stage I Colon Cancer; Stage II Colon Cancer; Stage III Colon Cancer

Keywords

Colorectal Neoplasms; Circulating Tumor DNA; ctDNA; Molecular Residual Disease; MRD; Driver Mutation; KRAS; BRAF; PIK3CA; Recurrence-Free Survival; Prognostic Biomarker; Postoperative Surveillance; Prospective Cohort; Multicenter Study

Outcome Measures

Primary Outcomes (1)

• Correlation between postoperative ctDNA-MRD status and Recurrence-Free Survival (RFS)

  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 Outcomes (3)

• Correlation between ctDNA-MRD status and Overall Survival (OS)

  3 years post curative resection

• Median lead time of MRD positivity prior to radiologically confirmed tumor recurrence

  Up to 3 years postoperative follow-up

• Association between dynamic ctDNA-MRD changes and adjuvant chemotherapy efficacy

  3 years post curative resection

Other Outcomes (2)

• MRD positive detection rate stratified by distinct oncogenic driver mutation subtypes

  All serial blood testing time points within 3-year follow-up

• Prognostic predictive performance of ctDNA-MRD across different driver mutation subtypes

  3 years post curative resection

Study Arms (1)

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

Interventions

Longitudinal ctDNA-MRD NGS testing at scheduled postoperative time points OTHER

biomarker test only

Driver-mutant Stage I-III Resectable Colon Adenocarcinoma Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Received neoadjuvant chemotherapy, radiotherapy or targeted therapy before surgery
• History of other malignant tumors (excluding non-adenomatous colorectal neoplasms)
• Pregnant or breastfeeding women
• 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)
• Abnormal laboratory values or social/family factors judged by investigator to impede sample collection and follow-up
• Simultaneous participation in other interventional clinical trials with mandatory assigned postoperative treatment regimen

Sponsors & Collaborators

• Ruijin Hospital: lead
• The First Hospital of Jilin University: collaborator

Study Sites (1)

Ruijin Hospital North

Shanghai, Shanghai Municipality, 201801, China

RECRUITING

Related Publications (5)

• Tie J, et al. Circulating tumor DNA dynamics predict recurrence and adjuvant chemotherapy benefit in colorectal cancer. N Engl J Med. 2020;382(6):545-555.

  BACKGROUND

• Liu Y, et al. Genomic characteristics of resectable colorectal cancer and their impact on ctDNA MRD detection. Clin Cancer Res. 2025;31(12):2456-2467.

  BACKGROUND

• BESPOKE Study Group. ctDNA MRD predicts recurrence and adjuvant chemotherapy benefit in stages II-III colorectal cancer. Lancet Oncol. 2025;26(5):689-701.

  BACKGROUND

• Chinese Society of Pathology; Pathology Quality Control Center; Colorectal Cancer Expert Committee of Chinese Society of Clinical Oncology (CSCO). [Clinical practice guideline for molecular pathology in colorectal cancer (2025 version)]. Zhonghua Bing Li Xue Za Zhi. 2025 May 8;54(5):448-462. doi: 10.3760/cma.j.cn112151-20241206-00827. Chinese.

  PMID: 40302573 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral whole blood and plasma will be collected. Cell-free DNA (cfDNA), including circulating tumor DNA (ctDNA), will be isolated for next-generation sequencing (NGS)-based molecular residual disease (MRD) testing. Residual samples will be destroyed after testing in accordance with the laboratory's standard operating procedure.

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Hereditary Sensory and Autonomic Neuropathies

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; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Central Study Contacts

Ren Zhao, MD, PhD

CONTACT

+86 18917762018; zhaorensurgeon@aliyun.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 23, 2026
• First Posted: August 31, 2026
• Study Start: August 14, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.

Locations

CN (1)