Using plasma ctDNA methylation to guide adjuvant chemotherapy for high-risk T3N0 colorectal cancer

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

This will test whether a blood ctDNA methylation test can help choose stronger chemotherapy after surgery for people with high-risk T3N0 (stage II) colorectal cancer who are ctDNA-positive one month after surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 340 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT07562711 on ClinicalTrials.gov

What this trial studies

This Phase 2 randomized study enrolls patients with high-risk T3N0 (stage II) colorectal cancer who are positive for plasma ctDNA methylation one month after surgery. Eligible patients are randomized to different adjuvant chemotherapy regimens (capecitabine-based or FOLFOX-based) with the goal of comparing ctDNA clearance rates. Serial ctDNA methylation testing is used to track molecular response and prognosis, and treatment escalation is applied early for those with persistent ctDNA. The study is conducted at Fudan University Shanghai Cancer Center and focuses on whether intensified adjuvant therapy improves molecular and clinical outcomes.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed high-risk T3N0 (stage II) colorectal cancer who are ctDNA-positive one month after surgery, have ECOG 0–2, and can provide informed consent are the intended candidates.

Not a fit: Patients who are ctDNA-negative after surgery, who received neoadjuvant therapy, who have recent other malignancies, are pregnant, or who cannot tolerate chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, using postoperative ctDNA methylation to guide and escalate adjuvant chemotherapy could reduce recurrence by identifying and treating patients with residual microscopic disease earlier.

How similar studies have performed: Previous randomized trials have shown promise for ctDNA-guided adjuvant strategies, but using plasma ctDNA methylation specifically to drive early chemotherapy escalation is a newer approach with limited direct prior evidence.

Eligibility criteria

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.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Guoxiang Cai

Conditions: ctDNA, Chemotherapy, Colorectal Cancer