Intensified chemotherapy for colon cancer based on ctDNA results

A Randomized Controlled Phase III Trial of Treatment Intensification in Stage II-III Colon Cancer Patients With Positive MRD During Adjuvant Chemotherapy

This study is testing if a stronger chemotherapy treatment can help people with stage 2-3 colon cancer who still have signs of cancer after standard treatment live longer and stay cancer-free.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 236 (estimated)
• Ages: 19 Years to 75 Years
• Sex: All
• Sponsor: Seoul National University Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Goyang and 2 other locations)
• Trial ID: NCT05534087 on ClinicalTrials.gov

What this trial studies

This phase 3 clinical trial investigates whether early intensified chemotherapy using modified FOLFIRINOX can improve disease-free survival rates in patients with stage 2-3 colon cancer who have detectable minimal residual disease (MRD) after standard adjuvant chemotherapy. The study is part of a larger platform that monitors circulating tumor DNA (ctDNA) to identify patients at high risk of relapse. Participants will be randomized to receive either the intensified chemotherapy or continue with standard treatment. The goal is to determine if the intensified approach can lead to better long-term outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 19 to 75 with stage 2-3 colon cancer who have positive ctDNA MRD after standard chemotherapy.

Not a fit: Patients with early-stage colon cancer or those whose ctDNA MRD is negative after standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with high-risk colon cancer.

How similar studies have performed: Other studies utilizing ctDNA for monitoring and treatment decisions in cancer have shown promising results, suggesting this approach may be effective.

Eligibility criteria

Inclusion Criteria:

1. Patients who willingly consented and signed the informed consent form to participate in the study
2. Age range of 19 to 75 years
3. Adenocarcinoma of colon confirmed by histology
4. Patients with stage II-III colon cancer as defined by the American Joint Committee on Cancer's eighth edition (Stage II cancer is limited to patients who are at a high risk, with more than one risk factor for recurrence.)
5. Patients who have completed the sixth cycle of FOLFOX or the fourth cycle of CAPOX adjuvant chemotherapy for colon cancer following radical resection (R0 resection)
6. A ctDNA test performed 3 to 6 weeks after surgery reveals a positive MRD
7. ECOG performance scale of 0-1 (only 1 is allowed for 70-75 years old)
8. Adequate bone marrow function \[ANC ≥1,300/LL, platelets ≥75,000/LL, hemoglobin ≥8.0g/dL (may be eligible in study if intermittent transfusion is required)\]
9. Appropriate liver function (total bilirubin ≤1.5xULN, AST and ALT ≤3xULN)
10. Appropriate renal function (serum creatine ≤1.5xULN, renal clearance rate ≥50 ml/min)
11. Patients who are deemed to understand the study protocol and are willing to participate in the trial until it is completed

Exclusion Criteria:

1. Pregnant or lactating women
2. Pregnant women who had a positive pregnancy test at the time of the baseline examination (postmenopausal women must be amenable for at least 12 months to be considered non-fertility)
3. Sexually active men and women of reproductive age who are unwilling to use contraception throughout the study treatment and for a period of 6 months (female) or 3 months (male) following the discontinuation of study treatment
4. Clinically significant heart condition \[unstable angina requiring medication, symptomatic coronary artery disease, congestive heart failure, or significant heart arrhythmia above NYHA II, or acute coronary syndrome, including myocardial infarction within the last 6 months\]
5. Active viral infections such as HIV (However, HBV carriers may enroll if their HBV DNA titer is less than 20,000 IU/ml, and antiviral drugs for hepatitis B may be administered prophylactically at the investigator's discretion)
6. Significant uncontrolled infections or other uncontrolled comorbidities
7. Symptomatic inflammatory bowel disease
8. Allogeneic transplantation history necessitating immunosuppressive therapy
9. A history of other malignancies identified within the last three years, except for completed removed basal cell carcinoma of the skin, completely removed cervical epithelial carcinoma, and thyroid cancer that has been treated, including surgery
10. Recurrent or residual disease identified clinically or radiographically
11. Previous history of irinotecan treatment
12. Polyposis including familial adenomatous polyps
13. Two or more colon or rectal cancers with a pathologic stage greater than II that were detected concurrently or within the last three years
14. When the investigator determines that the subjects' safety may be jeopardized during the study because of other serious or unstable pre-existing medical or mental conditions
15. Prior clinical trial participation and usage of investigational drugs or devices following radical resection of colon cancer
16. Patients with peripheral neuropathy who have a CTCAE v5 grade 3 or higher functional disability (corresponds to "severe symptoms, limiting self-care activity of daily living" according to CTCAE v5 criteria)
17. Previous anaphylactic reaction or severe and unexpected reactions to fluoropyrimidines or platinum
18. Gilbert's syndrome, dehydro-pyridine dehydrogenase (DPD) deficiency, or homozygous UGT1A1\*28 alleles

Where this trial is running

Goyang and 2 other locations

• National Cancer Center — Goyang, South Korea (Recruiting)
• Jin Won Kim — Seongnam, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)

Study contacts

• Principal investigator: Sae-Won Han, MD,PhD — Seoul National University Hospital South Korea
• Study coordinator: Sae-Won Han, MD,PhD

Conditions Colon Cancer; Minimal residual disease; Intensified chemotherapy