Plasma ctDNA methylation-guided adjuvant chemotherapy for stage I / low-risk stage II colorectal cancer

A Randomized Controlled Trial of Plasma ctDNA Methylation-Guided Adjuvant Chemotherapy Decisions in Postoperative Stage I or Low-Risk Stage II Colorectal Cancer Patients

This trial will test whether using a blood test for ctDNA methylation one month after surgery to guide adjuvant chemotherapy (such as capecitabine) helps clear ctDNA and lower recurrence risk in adults with stage I or low-risk stage II colorectal cancer who are ctDNA-positive.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT07562659 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial uses plasma ctDNA methylation testing one month after surgery to identify patients with stage I or low-risk stage II colorectal cancer who remain ctDNA-positive. Eligible patients are randomized to adjuvant chemotherapy regimens guided by ctDNA results, with capecitabine included as an intervention, to compare ctDNA clearance rates between arms. The study monitors serial blood samples for ctDNA methylation and follows clinical outcomes including recurrence. The goal is to determine whether early treatment escalation for ctDNA-positive patients increases ctDNA clearance and improves prognosis.

Who should consider this trial

Good fit: Adults (≥18) with surgically treated stage I or low-risk stage II colorectal cancer who are ctDNA-positive one month after surgery, have ECOG performance status 0–2, and can provide informed consent are ideal candidates.

Not a fit: Patients who are ctDNA-negative after surgery, those with poor performance status, pregnant or breastfeeding individuals, or those who received disqualifying prior treatments or cannot receive/attend adjuvant chemotherapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could personalize adjuvant treatment by identifying patients at higher recurrence risk and improving ctDNA clearance and long-term outcomes through earlier intensified therapy.

How similar studies have performed: Other ctDNA-guided adjuvant approaches (for example the DYNAMIC trial using tumor-informed assays) have shown promising results in stage II colon cancer, but methylation-based postoperative guidance is a newer approach with more limited prospective evidence.

Eligibility criteria

Inclusion Criteria:

Participants must meet all of the following 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; 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, Adjuvant Chemotherapy