Plasma ctDNA methylation–guided adjuvant chemotherapy for high-risk stage III colorectal cancer

A Randomized Controlled Trial of Plasma ctDNA Methylation-Guided Adjuvant Chemotherapy Decision-Making in High-Risk Stage III (T4N+ or T1-3N2) Colorectal Cancer

This trial will test whether adding bevacizumab to standard FOLFOX or CAPOX chemotherapy based on plasma ctDNA results helps adults with high-risk stage III colorectal cancer (T4N+ or T1-3N2).

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: bevacizumab
• Locations: 1 site (Shanghai)
• Trial ID: NCT07562490 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial enrolls adults with high-risk stage III colorectal cancer who are ctDNA-positive one month after surgery and assigns them to standard adjuvant chemotherapy (FOLFOX/CAPOX for 6 months) or the same chemotherapy plus bevacizumab for 6 months. Venous blood samples are collected at 1, 3, and 6 months postoperatively to monitor dynamic changes in plasma ctDNA methylation. Treatment decisions are guided by postoperative ctDNA status and patients are followed for treatment response and clinical outcomes. The trial is conducted at Fudan University Shanghai Cancer Center.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed high-risk stage III colorectal cancer (T4N+ or T1-3N2) who are ctDNA-positive one month after surgery and can receive FOLFOX/CAPOX are ideal candidates.

Not a fit: Patients who are ctDNA-negative after surgery, cannot tolerate bevacizumab or standard chemotherapy, or who received neoadjuvant therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce cancer recurrence by identifying patients with molecular residual disease who may benefit from adding bevacizumab to standard adjuvant chemotherapy.

How similar studies have performed: Using postoperative ctDNA to guide adjuvant therapy is an emerging approach with several trials showing ctDNA predicts recurrence, but the benefit of adding bevacizumab in this specific adjuvant, ctDNA-guided setting is not well established.

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