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

Circulating Tumor DNA Methylation Guided Postoperative Adjuvant Chemotherapy for High-risk Stage II/III Colorectal Cancer: A Multicenter, Prospective, Randomized Controlled Cohort Study (FINE Trial)

This study is testing whether using a blood test to check for cancer DNA can help doctors choose the best chemotherapy for patients with high-risk colorectal cancer after surgery to improve their chances of recovery.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 340 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05954078 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of adjuvant chemotherapy guided by circulating tumor DNA (ctDNA) methylation levels in patients with high-risk stage II and III colorectal cancer. Patients who have undergone surgery for colorectal adenocarcinoma and tested positive for ctDNA methylation will receive either mFOLFIRINOX or mFOLFOX6/XELOX chemotherapy regimens. The study aims to improve postoperative outcomes and reduce recurrence rates in this high-risk population. By tailoring chemotherapy based on ctDNA status, the trial seeks to enhance treatment efficacy and patient survival rates.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with high-risk stage II or III colorectal cancer who have undergone radical surgery and tested positive for ctDNA methylation.

Not a fit: Patients with low-risk colorectal cancer or those who have not undergone surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates and reduce recurrence in high-risk colorectal cancer patients.

How similar studies have performed: Other studies have shown promising results using ctDNA as a biomarker for treatment guidance, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

Patients who have been histopathologically diagnosed with colorectal adenocarcinoma;

Patients who have undergone radical curative resection of the primary tumors;

Patients with CRC of high-risk stage II and stage III based on final findings (UICC TNM Classification, 8th Edition);

Patients who tested positive for ctDNA methylation at 5-7 days after surgery prior to enrollment;

Patients with no obvious relapse confirmed by chest, abdominal, and pelvic CT scans, etc.;

Patients aged ≥ 18 and ≤80 years old, regardless of gender;

Patients with expected survival of more than 12 months;

Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1;

Patients who have no severe disorder in major organs (such as the bone marrow, heart, lungs, liver, and kidneys) and meet the following criteria: Neutrophil count ≥ 1,500/mm3, Platelet count ≥ 100,000/mm3, Hemoglobin ≥ 8.0 g/dL, Serum creatinine ≤ 1.5 mg/dL, Total bilirubin ≤ 1.5 mg/dL, ALT and AST ≤ 100 U/L

Patients with no diarrhea or stomatitis of Grade 2 or severer according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0;

Patients who voluntarily gave written consent to participate in the trial after receiving a thorough explanation of the trial before enrolling in the trial

Exclusion Criteria:

Neoadjuvant therapy performed before operation;

Blood transfusion performed during operation or within 2 weeks before operation;

Incomplete baseline samples, including preoperative plasma samples and plasma samples 5-7 days after operation;

Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;

Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;

Primary brain tumor or central nerve metastasis is not under control, with obvious intracranial hypertension or neuropsychiatric symptoms;

Patients with the following serious or uncontrollable diseases: severe heart disease, the condition is still unstable after treatment, including myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment; definite neuropathy or psychosis, including dementia or seizures; severe or uncontrolled infection; active disseminated intravascular coagulation and obvious bleeding tendency;

Significant impairment of important organ function;

Other conditions in which the investigator believes that the patient should not participate in this trial

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions High-risk Stage II Colorectal Cancer; Stage III Colorectal Cancer; Circulating Tumor DNA Methylation