Platform Study of Circulating Tumor DNA Directed Adjuvant Chemotherapy in Colon Cancer

• Status: Not yet recruiting
• Trial end date: 2030-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This study is a prospective, open-label, randomized phase 3 clinical trial. It aims to investigate if the early introduction of intensified chemotherapy (3 months of modified FOLFIRINOX followed by three months of FOLFIRI) improves the 3-year disease-free survival rate compared to standard treatment (FOLFOX/CAPOX for an additional three months to complete six months of standard adjuvant chemotherapy) in patients with stage 2-3 colon cancer in whom ctDNA MRD in the part 1 study remained positive during adjuvant FOLFOX/CAPOX chemotherapy

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seoul National University Hospital

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 three months following surgery (P3) reveals a positive MRD

7. At least four cycles of FOLFOX or three cycles of CAPOX prior to P3 ctDNA testing

8. ECOG performance scale of 0-1 (only 1 is allowed for 70-75 years old)

9. 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)]

10. Appropriate liver function (total bilirubin ≤1.5xULN, AST and ALT ≤3xULN)

11. Appropriate renal function (serum creatine ≤1.5xULN, renal clearance rate ≥50 ml/min)

12. 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)