TABLE 2.

Eligibility criteria of the VEGA trial

Inclusion criteria

1.Histopathological diagnosis has been made as primary colonic adenocarcinoma 2.Based on the operative findings and resected specimen findings, the primary location of the tumor is the colon* (does not include the appendix, rectum, and anal canal) *Includes the rectosigmoid part defined in the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, Ninth Edition 3. A colectomy including systematic lymph node dissection of D2 or D3 has been performed 4. At the time of completion of surgery, residual cancer is considered to be R0 5. The disease stage based on overall findings is high‐risk stage II (having at least one of the following risk factors [a] to [f] for relapse) or low‐risk stage III (T1‐3N1) (UICC TNM Classification, 8th Edition)* *N1c (UICC TNM Classification, 8th Edition) is also considered to be eligible (tumor deposits, or satellite nodules, are seen in the adjacent soft tissues of the colon or rectum without subserosal layer or peritoneal coat, but no regional lymph node metastasis). (a) T4 (SE/SI/AI), (b) Intestinal tract obstruction (clinical), (c) Intestinal tract perforation/penetration (clinical), (d) <12 dissected lymph nodes, (e) Poorly differentiated adenocarcinoma, signet‐ring cell carcinoma, or mucinous carcinoma, (f) Positive for lymphatic invasion, venous invasion, or neuroinvasion 6. Positive ctDNA within 4 wk preoperatively and negative ctDNA at 28 d ± 7 d postoperatively *The results of ctDNA testing are based on the test results in the GALAXY study (UMIN000039205) 7. Test using tumor samples shows BRAF V600E wild type 8. Microsatellite stable or proficient mismatch repair based on tumor testing 9. Enrollment can be performed within 8 wk after the curative resection, and treatment can be started within 2 wk after enrollment 10. The age at the time of acquisition of informed consent is 20 y or older 11. Eastern Cooperative Oncology Group Performance Status 0 or 1 12. No history of chemotherapy, immunotherapy, or radiotherapy within 6 mo prior to enrollment, including treatment for other types of cancer 13. The organ function is met according to the following laboratory values measured within 14 d prior to enrollment ‐ Neutrophil count ≥1500/mm3 ‐ Platelet count ≥100 000/mm3 ‐ Creatinine clearance ≥30 mL/min ‐ Total bilirubin ≤2.0 mg/dL ‐ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤100 IU/ ‐ Carcinoembryonic antigen ≤10 ng/mL 14. Voluntary consent to participation in the study has been obtained

Exclusion criteria

1.There are two or more infiltrating cancers of the large intestine origin at the same time. An infiltrating cancer is defined as cancer infiltrating to the submucosa or deeper, and does not include intramucosal cancer 2.History of a malignant tumor 3.Pregnant or breastfeeding women 4.Women of childbearing potential and men with reproductive capacity* *Men and women who agreed to use contraception during and up to 30 d after the treatment with CAPOX and understand the risks with pregnancy may be enrolled 5. Patients with complications of uncontrolled infections 6. Patients with peripheral sensory/motor neuropathy 7. Patients with complications of uncontrolled diabetes 8. Patients with complications of uncontrolled congestive heart failure, angina, hypertension, or arrhythmia 9. Continuous systemic administration of steroids (≥10 mg/d of prednisolone equivalent) (either oral or IV administration) 10. History or complication of neurologically or mentally significant illness 11. Positive HBs antigen or positive HCV antibody 12. Positive HIV antibody (a patient may enroll even if HIV antibody has not been tested) 13. Known deficiency of DPD 14. History of allergy to oxaliplatin and/or capecitabine 15. Any other cases which are judged to be inappropriate for participation in this clinical study by a physician

Abbreviations: ctDNA, circulating tumor DNA; DPD, dihydoropyrimidine dehydrogenase.