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

NCT07562711 | Recruiting Phase 2

• 2 other identifiers: 2410-Exp101U25A20115
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Cancer; ctDNA; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• ctDNA-clearance Rate

  3 months after initiation of adjuvant therapy.

Study Arms (2)

Single-agent chemotherapy group

ACTIVE COMPARATOR

The control group will receive postoperative capecitabine monotherapy for 6 months.

Drug: Capecitabine

doublet chemotherapy group

EXPERIMENTAL

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)

Interventions

Capecitabine DRUG

capecitabine for 6 months

Single-agent chemotherapy group

FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) DRUG

FOLFOX/CAPOX for 3 months; if ctDNA remains positive, switch to FOLFIRI.

doublet chemotherapy group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, regardless of sex;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, with an expected survival of \>3 months;
• Histologically confirmed postoperative pTNM stage high-risk stage II colorectal cancer;
• Positive ctDNA status at 1 month after surgery;
• Expected survival of \>12 months;
• 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.

You may not qualify if:

• Receipt of neoadjuvant therapy prior to surgery;
• Blood transfusion during surgery or within 2 weeks prior to surgery;
• Pregnant or breastfeeding women, or individuals of reproductive potential who are not using adequate contraception;
• History of other malignancies within the past 5 years, except for adequately treated carcinoma in situ of the cervix or non-melanoma skin cancer;
• Uncontrolled primary brain tumors or central nervous system metastases, or presence of significant intracranial hypertension or neuropsychiatric symptoms;
• 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;
• Any other condition that, in the opinion of the investigator, would make the patient unsuitable for participation in this study.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Capecitabine; Folfox protocol; Fluorouracil; Leucovorin; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Central Study Contacts

Guoxiang Cai

CONTACT

86-18017312703; gxcaifuscc@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fudan University Shanghai Cancer Center

Study Record Dates

• First Submitted: April 25, 2026
• First Posted: May 1, 2026
• Study Start: November 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)