Randomized Study of Plasma ctDNA Methylation to Guide Adjuvant Chemotherapy Decisions in High-Risk T3N0 Colorectal Cancer (CLEAR-02)

This study will utilize ctDNA methylation detection to evaluate patients with high-risk T3N0 stage II colorectal cancer who are ctDNA-positive one month after surgery. It aims to investigate the impact of different adjuvant chemotherapy regimens on ctDNA clearance rates and their prognostic significance. By using postoperative ctDNA status to identify patients at high risk of recurrence, the study seeks to implement intensified chemotherapy strategies (treatment escalation) at an early stage, thereby improving ctDNA clearance and ultimately enhancing patient outcomes

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Chemotherapy; ctDNA
• Intervention / Treatment: Drug: Capecitabine; Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

Detailed Description

This study will utilize ctDNA methylation detection to evaluate patients with high-risk T3N0 stage II colorectal cancer who are ctDNA-positive one month after surgery. It aims to investigate the impact of different adjuvant chemotherapy regimens on ctDNA clearance rates and their prognostic significance. By using postoperative ctDNA status to identify patients at high risk of recurrence, the study seeks to implement intensified chemotherapy strategies (treatment escalation) at an early stage, thereby improving ctDNA clearance and ultimately enhancing patient outcomes

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Guoxiang Cai; Phone Number: 86-18017312703; Email: gxcaifuscc@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Guoxiang Cai; Phone Number: 86-18017312703; Email: gxcaifuscc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years, regardless of sex;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of >3 months;
3. Histologically confirmed postoperative pTNM stage high-risk stage II colorectal cancer;
4. Positive ctDNA status at 1 month after surgery;
5. Expected survival of >12 months;
6. Ability to understand and willingness to sign a written informed consent form (personally or via a legally authorized representative/guardian), indicating that the subject understands the study objectives and required procedures and agrees to participate.

Exclusion Criteria:

1. Receipt of neoadjuvant therapy prior to surgery;
2. Blood transfusion during surgery or within 2 weeks prior to surgery;
3. Pregnant or breastfeeding women, or individuals of reproductive potential who are not using adequate contraception;
4. History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer;
5. Uncontrolled primary brain tumors or central nervous system metastases, or presence of significant intracranial hypertension or neuropsychiatric symptoms;
6. Presence of severe or uncontrolled comorbidities, including but not limited to:Severe cardiac disease that remains unstable despite treatment, including myocardial infarction, congestive heart failure, unstable angina, symptomatic pericardial effusion, or unstable arrhythmia within 6 months prior to enrollment; Clearly diagnosed neurological or psychiatric disorders, including dementia or seizure disorders;Severe or uncontrolled infections;Active disseminated intravascular coagulation (DIC) or significant bleeding tendency;Significant impairment of major organ function;
7. Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single-agent chemotherapy group; The control group will receive postoperative capecitabine monotherapy for 6 months.	Drug: Capecitabine; capecitabine for 6 months
Experimental: doublet chemotherapy group; The intervention group will receive FOLFOX or CAPOX for 3 months. After 3 months of treatment, ctDNA status will be reassessed. Patients who convert to ctDNA-negative will receive capecitabine monotherapy for an additional 3 months, whereas those who remain ctDNA-positive will switch to FOLFIRI or CAPIRI for a further 3 months.	Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin); FOLFOX/CAPOX for 3 months; if ctDNA remains positive, switch to FOLFIRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's 2-year Progression-Free Survival	Two-year Progression-Free Survival (PFS) is defined as the proportion of patients who remain alive without evidence of disease progression or recurrence within 24 months from the date of surgery (or randomization, as specified in the protocol). Disease progression is determined according to radiologic, clinical, or pathological criteria.	2-year Progression-Free Survival

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA-clearance Rate	ctDNA clearance rate is defined as the proportion of patients with detectable circulating tumor DNA (ctDNA) at baseline who achieve conversion to undetectable ctDNA at a predefined post-treatment time point, as assessed by the specified ctDNA assay.	3 months after initiation of adjuvant therapy.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 25, 2026
• First Submitted That Met QC Criteria: April 25, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 25, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Capecitabine; Oxaliplatin; Fluorouracil; Leucovorin; Folfox protocol
• Other Study ID Numbers: 2410-Exp101; U25A20115 (Other Grant/Funding Number: National Natural Science Foundation of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No