Neoadjuvant CAPEOX Versus Upfront Surgery for Locally Advanced Colon Cancer With Elevated CEA: A Single-Center, Open-Label, Randomized Controlled Trial

Summary

The goal of this interventional clinical trial is to compare the efficacy of neoadjuvant chemotherapy versus upfront surgery in adults aged 18-70 years with stage II (high-risk)-III, non-MSI-H colon adenocarcinoma and elevated baseline CEA (\>5 ng/mL) undergoing curative-intent treatment. This single-center, open-label, randomized controlled study will evaluate 2-year disease-free survival (2y-DFS) as the primary endpoint, with all study-related procedures-including longitudinal ctDNA-based molecular residual disease (MRD) monitoring, Immunoscore assessment, tumor tissue sequencing, and surveillance imaging-provided at no cost to participants. The main questions it aims to answer are:

* Does a treatment strategy involving neoadjuvant CAPOX followed by surgery improve 2y-DFS compared with upfront surgery followed by standard adjuvant chemotherapy?
* Do postoperative ctDNA-MRD status and its longitudinal dynamics predict 2y-DFS?
* Does combining ctDNA-MRD with Immunoscore enhance prognostic risk stratification for recurrence beyond either biomarker alone?

Participants will:

* Be randomized 1:1 (N=100) to one of two treatment pathways:

* Arm A: Neoadjuvant CAPOX × 4 cycles → curative surgery (R0 planned) → postoperative management per standard practice
* Arm B: Upfront curative surgery → postoperative standard adjuvant chemotherapy per guideline → routine surveillance
* Undergo baseline assessments prior to treatment initiation, including blood draw, colonoscopy, primary tumor next-generation sequencing (for personalized ctDNA-MRD assay development), and Immunoscore testing-all provided free of charge as part of the study.
* Provide postoperative blood samples for ctDNA-MRD testing at approximately postoperative day \~7 and day \~30 (before adjuvant therapy start, if applicable).
* During follow-up, provide serial blood samples every 3 months, aligned with routine surveillance visits, for repeat ctDNA-MRD analysis.
* Receive standard-of-care postoperative surveillance (including imaging and clinical evaluations) through 2 years, with all study-mandated assessments covered by the trial.

This trial integrates clinical intervention with comprehensive biomarker profiling to determine whether early systemic therapy alters MRD dynamics and improves outcomes in high-risk, CEA-elevated colon cancer.

Conditions

• Minimal Residual Disease
• Immunoscore
• Neoadjuvant Chemotherapy
• Colon Cancer (Stage II &Amp; III)

Interventions

DIAGNOSTIC_TEST

ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment

This study uses personalized circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) monitoring together with tumor immune profiling (Immunoscore) for postoperative risk stratification. At baseline, primary tumor tissue obtained by endoscopy and/or surgery undergoes next-generation sequencing/whole-exome sequencing to identify patient-specific somatic variants and to build an individualized ctDNA MRD assay panel. Peripheral blood is collected at baseline, approximately postoperative day 7, postoperative day 30 (before adjuvant therapy when feasible), and every 3 months during routine follow-up for serial MRD testing (MRD positive/negative and longitudinal changes). Immunoscore is assessed from resected tumor tissue using a standardized, validated workflow to quantify intratumoral and invasive-margin immune cell densities and is categorized per assay reporting. MRD status and Immunoscore are integrated to define biomarker-based recurrence risk groups and correlated with cli

DRUG

Neoadjuvant Chemotherapy

In ARM A, patient receive neoadjuvant CAPEOX chemotherapy for 4 cycles before surgery.

DRUG

Adjuvant chemotherapy

The application of post-operative adjuvant chemotherapy depends on the final pathological staging, under the guidance of the NCCN/ESMO/CSCO guidelines for colorectal cancer.

Sponsors & Collaborators

• Sun Yat-sen University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-24

Primary Completion

2027-02-28

Completion

2027-07-31