Plasma ctDNA methylation-guided adjuvant chemotherapy for people with T4N0 and low‑risk stage III colorectal cancer.

Randomized Trial of Plasma ctDNA Methylation-Guided Adjuvant Therapy in T4N0 and Low-Risk Stage III Colorectal Cancer

This trial will test whether using a blood test (plasma ctDNA methylation) to guide 3 vs 6 months of adjuvant chemotherapy or to switch regimens helps people with T4N0 or low‑risk stage III colorectal cancer after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 340 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Locations: 1 site (Shanghai)
• Trial ID: NCT07562503 on ClinicalTrials.gov

What this trial studies

This randomized phase 2 trial enrolls patients with T4N0 or low‑risk stage III colorectal cancer who are ctDNA‑positive one month after surgery and randomizes them to a control or intervention arm. The control arm receives standard adjuvant chemotherapy (FOLFOX or CAPOX) for 3 months, while the intervention arm receives either 6 months of FOLFOX/CAPOX or 3 months of FOLFOX/CAPOX followed by 3 months of FOLFIRI/CAPIRI guided by plasma ctDNA methylation results. Venous blood samples (8–16 mL) are collected at 1, 3, and 6 months postoperatively for dynamic ctDNA methylation monitoring to inform treatment decisions. The trial is conducted at Fudan University Shanghai Cancer Center and is designed to test whether methylation‑guided therapy can refine adjuvant treatment duration or regimen choice.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18 years) with histologically confirmed T4N0 or low‑risk stage III colorectal cancer who are ctDNA‑positive at 1 month after surgery and have ECOG performance status 0–2.

Not a fit: Patients who are ctDNA‑negative after surgery, who received neoadjuvant therapy, who are pregnant or breastfeeding, or who have recent other malignancies or poor performance status are less likely to benefit from this ctDNA‑guided approach.

Why it matters

Potential benefit: If successful, this approach could personalize adjuvant chemotherapy so some patients avoid unnecessary longer treatment while others receive intensified therapy when ctDNA indicates persistent disease.

How similar studies have performed: Other ctDNA‑guided adjuvant trials (for example DYNAMIC and CIRCULATE programs) have shown promising results for tailoring chemotherapy, but using ctDNA methylation patterns specifically to guide duration and regimen choice is still relatively novel.

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; Colorectal Cancer; Chemotherapy