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

NCT07413146 | Not Yet Recruiting DMC

• 1 other identifier: 2025-FXY-317
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief 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)

Keywords

advanced stage colon cancer; Minimal Residual Disease; Immunoscore; neoadjuvant chemotherapy; upfront surgery

Outcome Measures

Primary Outcomes (1)

• 2-year Disease-Free Survival (2y-DFS)

  Disease-free survival is defined as the time from curative-intent surgery to the first occurrence of any of the following events: (1) local recurrence, (2) distant metastasis, (3) a second primary colorectal cancer, or (4) death from any cause, whichever occurs first. Participants without an event will be censored at the last disease assessment.

  From date of surgery up to 24 months postoperatively.

Secondary Outcomes (2)

• 2-year Overall Survival (2y-OS)

  From date of surgery up to 24 months postoperatively.

• Local Recurrence Rate at 2 years

  Up to 24 months postoperatively.

Other Outcomes (1)

• Distant Metastasis Rate at 2 years

  Up to 24 months postoperatively.

Study Arms (2)

Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy

EXPERIMENTAL

Participants in this arm receive 4 cycles of standard neoadjuvant CAPOX (CAPEOX) prior to curative-intent surgery. Postoperative adjuvant chemotherapy is determined based on the postoperative pathologic stage and risk stratification (per current CSCO guideline criteria). High-risk stage III participants receive an additional 4 cycles of CAPOX. For low-risk stage III or stage II participants, either no additional adjuvant chemotherapy or an additional 4 cycles of capecitabine is administered, determined by the treating physician in discussion with the participant.

Diagnostic Test: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment; Drug: Neoadjuvant Chemotherapy; Drug: Adjuvant chemotherapy

Upfront R0-planned Surgery followed by adjuvant chemotherapy

ACTIVE COMPARATOR

In this arm, participants undergo upfront curative-intent (radical) surgery after standard preoperative assessment and staging. Postoperative adjuvant chemotherapy is administered per current CSCO guidelines based on pathologic stage and risk factors, with regimen selection determined by the treating physician in discussion with the patient.

Diagnostic Test: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment; Drug: Adjuvant chemotherapy

Interventions

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

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

Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy; Upfront R0-planned Surgery followed by adjuvant chemotherapy

Neoadjuvant Chemotherapy DRUG

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

Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy

Adjuvant chemotherapy DRUG

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.

Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy; Upfront R0-planned Surgery followed by adjuvant chemotherapy

Eligibility Criteria

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

You may qualify if:

• Participants must meet all of the following criteria:
• Age 18 to 70 years (inclusive) at the time of written informed consent. ECOG performance status 0-1, without deterioration within 2 weeks prior to enrollment; anticipated life expectancy ≥12 weeks.
• Histologically or cytologically confirmed colon adenocarcinoma, non-MSI-H/dMMR, with pathologic stage (AJCC/UICC TNM 8th edition) of:
• High-risk stage II, or Stage III. High-risk stage II features include: T4, poor/undifferentiated histology (high grade; excluding MSI-H), lymphovascular invasion, perineural invasion, preoperative bowel obstruction or tumor perforation, positive/unknown margin status, insufficient margin clearance, \<12 lymph nodes examined, or high-grade tumor budding.
• Tumor location consistent with colon cancer: distal tumor margin ≥12 cm from the anal verge on preoperative endoscopy.
• Baseline serum CEA \>5 ng/mL prior to treatment. No evidence of distant metastasis (distant organ and/or distant lymph node metastasis) based on comprehensive clinical evaluation.
• Ability to provide required clinical data for study collection. Ability to provide adequate fresh tumor tissue from endoscopy and/or surgery for WES/NGS to develop an individualized ctDNA MRD panel, and ability to provide required blood samples for ctDNA testing (baseline, postoperative \~day 7, postoperative \~day 30).
• Candidate for curative-intent R0 resection. Willing and able to comply with the protocol schedule, including regular follow-up visits and necessary treatments, and provides written informed consent.

You may not qualify if:

• Participants will be excluded if any of the following apply:
• Prior or concurrent other malignant tumor. Any severe comorbidity that, in the investigator's judgment, may significantly affect follow-up or short-term survival.
• Any other medical condition, or social/psychological circumstance, that in the investigator's judgment makes the participant unsuitable for the study.
• MSI-H/dMMR tumor. Evidence of metastatic disease by pathology, clinical assessment, or imaging, including isolated distant lesions, distant disease, or non-contiguous intraperitoneal metastasis.
• Multiple primary colon cancers. Underwent open surgery at a non-colon site within 14 days prior to enrollment. Unable to provide required tumor tissue for WES/NGS or personalized MRD panel development, personalized MRD panel customization failure, or unable to provide required blood samples (baseline, postoperative \~day 7, postoperative \~day 30).
• History of blood transfusion within 2 weeks prior to surgery or intraoperatively.
• Unable to undergo contrast-enhanced CT or MRI for routine clinical follow-up. Fever ≥38°C within the past 7 days, or clinically significant active infection (including active tuberculosis), or active fungal/bacterial/viral infection requiring systemic therapy.
• Inadequate bone marrow reserve or organ function meeting any of the following laboratory abnormalities (within 1 week prior to testing without corrective treatment):
• ANC \< 1.5 × 10⁹/L Platelets \< 90 × 10⁹/L Hemoglobin \< 90 g/L (\<9 g/dL) ALT \> 3 × ULN AST \> 3 × ULN or total bilirubin \> 1.5 × ULN Creatinine \> 1.5 × ULN or creatinine clearance \< 45 mL/min (Cockcroft-Gault) Albumin \< 28 g/L Pregnant or breastfeeding, or planning pregnancy during the study period. Any other condition that, in the investigator's judgment, indicates the participant should not participate.

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Neoplasm, Residual; Colonic Neoplasms

Interventions

Neoadjuvant Therapy; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Central Study Contacts

Rongxin Zhang, MD, PhD

CONTACT

+86 02087343920; zhangrx@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: Vice Director of Colorectal Surgery, Cheif Surgeon

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: February 24, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02