Minimal Residual DiseaseNCT07413146
Neoadjuvant CAPEOX Versus Upfront Surgery for Locally Advanced Colon Cancer With Elevated CEA: A Single-Center, Open-Label, Randomized Controlled Trial
A study testing ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment, Neoadjuvant Chemotherapy and Adjuvant chemotherapy in people with Minimal Residual Disease and Immunoscore, run by Sun Yat-sen University.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Minimal Residual Disease, Immunoscore, Neoadjuvant Chemotherapy
- What is being tested?
- ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment, Neoadjuvant Chemotherapy and Adjuvant chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 24 Feb 2026to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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?
Read more
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.
Read the detailed description
Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a leading cause of cancer-related mortality. In China, CRC incidence ranks among the top cancers, and CRC-related death constitutes a major public health burden. Approximately 80% of CRC patients present with non-metastatic disease (stages I-III), representing the primary population for whom recurrence prevention is critical. Despite guideline-recommended curative-intent surgery and perioperative systemic therapy, at least 30% of patients with resectable stage II-III colon cancer experience recurrence or distant metastasis after initial treatment. This underscores an urgent need for more effective therapeutic strategies and better tools for risk-adapted management.
Current adjuvant chemotherapy decisions for stage II (high-risk) and stage III colon cancer rely largely on TNM staging and clinicopathologic risk factors, which do not directly measure residual tumor burden. Consequently, some patients may be overtreated with unnecessary toxicity, while others at high risk of relapse may receive insufficient therapy. Elevated baseline carcinoembryonic antigen (CEA >5 ng/mL) is a well-established adverse prognostic factor in colon cancer and identifies a subgroup with higher recurrence risk. Emerging data also suggest that patients with proficient mismatch repair (pMMR)/non-MSI-H tumors-particularly those with elevated CEA-may benefit from early systemic intervention before surgery. Therefore, evaluating whether neoadjuvant chemotherapy improves outcomes compared with standard upfront surgery represents a clinically meaningful question in this high-risk population.
This trial is designed as a single-center, open-label, randomized controlled study to directly compare two perioperative treatment strategies in adults aged 18-70 years with stage II (high-risk)-III, non-MSI-H colon adenocarcinoma and baseline CEA >5 ng/mL. All participants will be randomly assigned (1:1) to either:
Arm A (Neoadjuvant CAPOX Pathway): 4 cycles of neoadjuvant CAPOX chemotherapy followed by curative-intent surgery (R0 planned), with postoperative management per standard guidelines; or Arm B (Upfront Surgery Pathway): immediate curative-intent surgery followed by standard adjuvant chemotherapy and routine surveillance.
The primary objective of the study is to determine whether the neoadjuvant approach improves 2-year disease-free survival (2y-DFS) compared with upfront surgery. Importantly, all study-mandated procedures-including tumor tissue sequencing, Immunoscore assessment, personalized ctDNA-MRD assay development, and serial blood-based MRD monitoring-are provided at no cost to participants as part of the research protocol.
In parallel, the study incorporates a comprehensive biomarker program to explore mechanisms of treatment response and refine recurrence prediction. Circulating tumor DNA (ctDNA)-defined molecular residual disease (MRD) reflects microscopic residual tumor burden at the molecular level. Postoperative ctDNA positivity has been consistently associated with high recurrence risk in CRC, and serial monitoring can detect molecular relapse weeks to months before radiologic evidence. Immunoscore (IS), which quantifies CD3+ and CD8+ T-cell densities in the tumor core and invasive margin, provides a robust measure of anti-tumor immunity and independently predicts outcomes in colon cancer. We hypothesize that integrating these complementary biomarkers may enhance risk stratification and reveal biological insights into how neoadjuvant therapy modulates MRD dynamics and immune contexture.
Study Objectives Primary Objective
- To compare 2-year disease-free survival (2y-DFS) between patients receiving neoadjuvant CAPOX followed by surgery versus those undergoing upfront surgery followed by standard adjuvant chemotherapy.
Secondary/Exploratory Objectives To evaluate the prognostic value of postoperative ctDNA-MRD status (at ~day 7 and ~day 30) and its longitudinal changes for predicting 2y-DFS.
To assess whether combining ctDNA-MRD with Immunoscore improves recurrence risk stratification beyond either biomarker alone.
To estimate 2-year overall survival (2y-OS), local recurrence rate, and distant metastasis rate in each treatment arm and across biomarker-defined subgroups.
To characterize the impact of neoadjuvant chemotherapy on ctDNA-MRD clearance rates and immune microenvironment features compared with upfront surgery.
Study Design This is a single-center, prospective, randomized (1:1), open-label clinical trial enrolling approximately 100 eligible participants. Randomization ensures balanced comparison of two clinically relevant pathways within a controlled framework, with treatment efficacy (2y-DFS) as the primary endpoint. While biomarker analyses are hypothesis-generating and secondary, they are prospectively integrated to support precision oncology applications.
Study Procedures and Assessments Baseline (prior to allocated treatment)
All participants will undergo standardized baseline evaluations, including:
Clinical assessment and eligibility confirmation (ECOG 0-1); Colonoscopy (as clinically indicated); Blood draw for baseline ctDNA analysis;
Tumor tissue collection (from diagnostic biopsy or surgical specimen) for:
- Whole-exome or targeted NGS to enable development of a personalized ctDNA-MRD assay;
- Immunoscore testing using a validated institutional platform. All biomarker-related assays are funded by the study. Treatment Phase Arm A: Neoadjuvant CAPOX × 4 cycles → curative surgery (R0 planned). Arm B: Upfront curative surgery → adjuvant chemotherapy per NCCN/ESMO guidelines.
All treatments follow institutional standards; adverse events are managed per routine care.
Postoperative ctDNA-MRD Sampling
Blood will be collected at key timepoints:
- Postoperative day 7
- Postoperative day 30 These samples enable early MRD assessment before adjuvant therapy initiation (when applicable).
Follow-up Phase Participants will undergo standard postoperative surveillance (imaging, labs, clinical visits) every 3 months through 2 years. Serial blood samples for ctDNA-MRD testing will be collected at each visit, synchronized with routine care. All imaging and study-related biospecimen analyses are covered by the trial.
Biomarker Strategy ctDNA-MRD will be assessed using a patient-specific NGS-informed panel, with results reported as positive/negative at each timepoint.
Immunoscore will be categorized as High, Intermediate, or Low per validated criteria.
Combined risk groups (e.g., ctDNA-/Immunoscore-High = lowest risk; ctDNA+/Immunoscore-Low = highest risk) will be evaluated for association with 2y-DFS and treatment response.
While biomarker results may inform clinical discussions, treatment decisions remain within standard-of-care discretion unless future protocol amendments specify otherwise.
Outcomes Primary Outcome 2-year Disease-Free Survival (2y-DFS): time from surgery to first recurrence (local/distant), second primary CRC, or death from any cause.
Secondary Outcomes 2-year Overall Survival (2y-OS) 2-year local recurrence and distant metastasis rates ctDNA-MRD detection rates, clearance kinetics, and prognostic performance alone and combined with Immunoscore Comparative analysis of MRD dynamics and immune profiles between treatment arms Statistical Considerations The primary analysis will compare 2y-DFS between arms using Kaplan-Meier estimates and log-rank tests. Cox regression models will adjust for key covariates (e.g., stage, lymphovascular invasion, treatment arm). Biomarker analyses will be exploratory but pre-specified, with model performance metrics (C-index, net reclassification improvement) used to assess added value of combined ctDNA/Immunoscore stratification.
Eligibility Criteria (Summary) Key Inclusion: Age 18-70; ECOG 0-1; histologically confirmed stage II (high-risk) or III, non-MSI-H colon adenocarcinoma; CEA >5 ng/mL; no metastasis; R0 resection planned; ability to provide tumor tissue and serial blood samples.
Key Exclusion: MSI-H/dMMR; metastatic/peritoneal disease; prior malignancy; major comorbidity; pregnancy; inability to undergo contrast imaging or provide biospecimens; MRD panel customization failure.
Participant Support A dedicated research team will coordinate follow-up visits, sample collection, and communication of biomarker results. All study-related diagnostics-including NGS, Immunoscore, and serial ctDNA-MRD tests-are provided free of charge, and reports will be shared with participants and treating clinicians to support informed decision-making alongside standard care.
- Conditions
- Minimal Residual Disease, Immunoscore, Neoadjuvant Chemotherapy, Colon Cancer (Stage II &Amp; III)
- Being tested
- ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment, Neoadjuvant Chemotherapy, Adjuvant chemotherapy
- Keywords
- advanced stage colon cancer, Minimal Residual Disease, Immunoscore, neoadjuvant chemotherapy, upfront surgery
- Medical subject headings
- Neoplasm, Residual, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore AssessmentDiagnostic 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 ChemotherapyDrug
In ARM A, patient receive neoadjuvant CAPEOX chemotherapy for 4 cycles before surgery.
Adjuvant chemotherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment; Drug: Adjuvant chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of surgery up to 24 months postoperatively.
Secondary outcomes (2)
2-year Overall Survival (2y-OS)
Overall survival is defined as the time from curative-intent surgery to death from any cause. Participants alive at the end of follow-up will be censored at the last known date alive.
Measured: From date of surgery up to 24 months postoperatively.
Local Recurrence Rate at 2 years
Proportion of participants who develop local recurrence (tumor recurrence at or adjacent to the primary tumor bed/anastomosis and/or regional sites consistent with local-regional relapse, as determined by standard clinical assessment and imaging/pathology when available) within 24 months after surgery.
Measured: Up to 24 months postoperatively.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start24 Feb 2026 (estimated)
- Primary completion28 Feb 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Minimal Residual DiseaseStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gong Chen, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07413146
- Sponsor's protocol ID
- 2025-FXY-317
- Status last verified
- Feb 2026
- First submitted
- 9 Feb 2026
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant CAPEOX Versus Upfront Surgery for Locally Advanced Colon Cancer With Elevated CEA: A Single-Center, Open-Label, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07413146
- Acronym / sponsor ID
- 2025-FXY-317
- 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
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 24 Feb 2026 (estimated)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 17 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Colorectal cancer (CRC) is one of the most common malignancies worldwide and remains a leading cause of cancer-related mortality. In China, CRC incidence ranks among the top cancers, and CRC-related death constitutes a major public health burden. Approximately 80% of CRC patients present with non-metastatic disease (stages I-III), representing the primary population for whom recurrence prevention is critical. Despite guideline-recommended curative-intent surgery and perioperative systemic therapy, at least 30% of patients with resectable stage II-III colon cancer experience recurrence or distant metastasis after initial treatment. This underscores an urgent need for more effective therapeutic strategies and better tools for risk-adapted management.
Current adjuvant chemotherapy decisions for stage II (high-risk) and stage III colon cancer rely largely on TNM staging and clinicopathologic risk factors, which do not directly measure residual tumor burden. Consequently, some patients may be overtreated with unnecessary toxicity, while others at high risk of relapse may receive insufficient therapy. Elevated baseline carcinoembryonic antigen (CEA >5 ng/mL) is a well-established adverse prognostic factor in colon cancer and identifies a subgroup with higher recurrence risk. Emerging data also suggest that patients with proficient mismatch repair (pMMR)/non-MSI-H tumors-particularly those with elevated CEA-may benefit from early systemic intervention before surgery. Therefore, evaluating whether neoadjuvant chemotherapy improves outcomes compared with standard upfront surgery represents a clinically meaningful question in this high-risk population.
This trial is designed as a single-center, open-label, randomized controlled study to directly compare two perioperative treatment strategies in adults aged 18-70 years with stage II (high-risk)-III, non-MSI-H colon adenocarcinoma and baseline CEA >5 ng/mL. All participants will be randomly assigned (1:1) to either:
Arm A (Neoadjuvant CAPOX Pathway): 4 cycles of neoadjuvant CAPOX chemotherapy followed by curative-intent surgery (R0 planned), with postoperative management per standard guidelines; or Arm B (Upfront Surgery Pathway): immediate curative-intent surgery followed by standard adjuvant chemotherapy and routine surveillance.
The primary objective of the study is to determine whether the neoadjuvant approach improves 2-year disease-free survival (2y-DFS) compared with upfront surgery. Importantly, all study-mandated procedures-including tumor tissue sequencing, Immunoscore assessment, personalized ctDNA-MRD assay development, and serial blood-based MRD monitoring-are provided at no cost to participants as part of the research protocol.
In parallel, the study incorporates a comprehensive biomarker program to explore mechanisms of treatment response and refine recurrence prediction. Circulating tumor DNA (ctDNA)-defined molecular residual disease (MRD) reflects microscopic residual tumor burden at the molecular level. Postoperative ctDNA positivity has been consistently associated with high recurrence risk in CRC, and serial monitoring can detect molecular relapse weeks to months before radiologic evidence. Immunoscore (IS), which quantifies CD3+ and CD8+ T-cell densities in the tumor core and invasive margin, provides a robust measure of anti-tumor immunity and independently predicts outcomes in colon cancer. We hypothesize that integrating these complementary biomarkers may enhance risk stratification and reveal biological insights into how neoadjuvant therapy modulates MRD dynamics and immune contexture.
Study Objectives Primary Objective
- To compare 2-year disease-free survival (2y-DFS) between patients receiving neoadjuvant CAPOX followed by surgery versus those undergoing upfront surgery followed by standard adjuvant chemotherapy.
Secondary/Exploratory Objectives To evaluate the prognostic value of postoperative ctDNA-MRD status (at ~day 7 and ~day 30) and its longitudinal changes for predicting 2y-DFS.
To assess whether combining ctDNA-MRD with Immunoscore improves recurrence risk stratification beyond either biomarker alone.
To estimate 2-year overall survival (2y-OS), local recurrence rate, and distant metastasis rate in each treatment arm and across biomarker-defined subgroups.
To characterize the impact of neoadjuvant chemotherapy on ctDNA-MRD clearance rates and immune microenvironment features compared with upfront surgery.
Study Design This is a single-center, prospective, randomized (1:1), open-label clinical trial enrolling approximately 100 eligible participants. Randomization ensures balanced comparison of two clinically relevant pathways within a controlled framework, with treatment efficacy (2y-DFS) as the primary endpoint. While biomarker analyses are hypothesis-generating and secondary, they are prospectively integrated to support precision oncology applications.
Study Procedures and Assessments Baseline (prior to allocated treatment)
All participants will undergo standardized baseline evaluations, including:
Clinical assessment and eligibility confirmation (ECOG 0-1); Colonoscopy (as clinically indicated); Blood draw for baseline ctDNA analysis;
Tumor tissue collection (from diagnostic biopsy or surgical specimen) for:
- Whole-exome or targeted NGS to enable development of a personalized ctDNA-MRD assay;
- Immunoscore testing using a validated institutional platform. All biomarker-related assays are funded by the study. Treatment Phase Arm A: Neoadjuvant CAPOX × 4 cycles → curative surgery (R0 planned). Arm B: Upfront curative surgery → adjuvant chemotherapy per NCCN/ESMO guidelines.
All treatments follow institutional standards; adverse events are managed per routine care.
Postoperative ctDNA-MRD Sampling
Blood will be collected at key timepoints:
- Postoperative day 7
- Postoperative day 30 These samples enable early MRD assessment before adjuvant therapy initiation (when applicable).
Follow-up Phase Participants will undergo standard postoperative surveillance (imaging, labs, clinical visits) every 3 months through 2 years. Serial blood samples for ctDNA-MRD testing will be collected at each visit, synchronized with routine care. All imaging and study-related biospecimen analyses are covered by the trial.
Biomarker Strategy ctDNA-MRD will be assessed using a patient-specific NGS-informed panel, with results reported as positive/negative at each timepoint.
Immunoscore will be categorized as High, Intermediate, or Low per validated criteria.
Combined risk groups (e.g., ctDNA-/Immunoscore-High = lowest risk; ctDNA+/Immunoscore-Low = highest risk) will be evaluated for association with 2y-DFS and treatment response.
While biomarker results may inform clinical discussions, treatment decisions remain within standard-of-care discretion unless future protocol amendments specify otherwise.
Outcomes Primary Outcome 2-year Disease-Free Survival (2y-DFS): time from surgery to first recurrence (local/distant), second primary CRC, or death from any cause.
Secondary Outcomes 2-year Overall Survival (2y-OS) 2-year local recurrence and distant metastasis rates ctDNA-MRD detection rates, clearance kinetics, and prognostic performance alone and combined with Immunoscore Comparative analysis of MRD dynamics and immune profiles between treatment arms Statistical Considerations The primary analysis will compare 2y-DFS between arms using Kaplan-Meier estimates and log-rank tests. Cox regression models will adjust for key covariates (e.g., stage, lymphovascular invasion, treatment arm). Biomarker analyses will be exploratory but pre-specified, with model performance metrics (C-index, net reclassification improvement) used to assess added value of combined ctDNA/Immunoscore stratification.
Eligibility Criteria (Summary) Key Inclusion: Age 18-70; ECOG 0-1; histologically confirmed stage II (high-risk) or III, non-MSI-H colon adenocarcinoma; CEA >5 ng/mL; no metastasis; R0 resection planned; ability to provide tumor tissue and serial blood samples.
Key Exclusion: MSI-H/dMMR; metastatic/peritoneal disease; prior malignancy; major comorbidity; pregnancy; inability to undergo contrast imaging or provide biospecimens; MRD panel customization failure.
Participant Support A dedicated research team will coordinate follow-up visits, sample collection, and communication of biomarker results. All study-related diagnostics-including NGS, Immunoscore, and serial ctDNA-MRD tests-are provided free of charge, and reports will be shared with participants and treating clinicians to support informed decision-making alongside standard care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy | Experimental | Diagnostic Test: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment, Drug: Neoadjuvant Chemotherapy, Drug: Adjuvant chemotherapyParticipants 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. |
| Upfront R0-planned Surgery followed by adjuvant chemotherapy | Active comparator | Diagnostic Test: ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment, Drug: Adjuvant chemotherapyIn 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore AssessmentThis 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 | Diagnostic test | Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy, Upfront R0-planned Surgery followed by adjuvant chemotherapy |
| Neoadjuvant ChemotherapyIn ARM A, patient receive neoadjuvant CAPEOX chemotherapy for 4 cycles before surgery. | Drug | Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy |
| Adjuvant chemotherapyThe application of post-operative adjuvant chemotherapy depends on the final pathological staging, under the guidance of the NCCN/ESMO/CSCO guidelines for colorectal cancer. | Drug | Neoadjuvant Chemotherapy before R0-planned Surgery ± adjuvant chemotherapy, Upfront R0-planned Surgery followed by adjuvant chemotherapy |
Primary outcome
2-year Disease-Free Survival (2y-DFS)
Time frame: From date of surgery up to 24 months postoperatively.
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.
2 secondary outcomes
2-year Overall Survival (2y-OS)
Time frame: From date of surgery up to 24 months postoperatively.
Local Recurrence Rate at 2 years
Time frame: Up to 24 months postoperatively.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing ctDNA-Based Molecular Residual Disease (MRD) Monitoring and Immunoscore Assessment, Neoadjuvant Chemotherapy and Adjuvant chemotherapy in people with Minimal Residual Disease and Immunoscore, run by Sun Yat-sen University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rongxin Zhang, MD, PhD (+86 02087343920, zhangrx@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year Disease-Free Survival (2y-DFS) (time frame: From date of surgery up to 24 months postoperatively.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.