Initial Attack on Latent Metastasis Using TAS-102 for ct DNA Identified Colorectal Cancer Patients After Curative Resection

A Randomized, Double-Blind, Phase III Study Comparing FTD/TPI Therapy Versus Placebo in Patients Who Are Positive for Blood Circulating Tumor DNA After Curative Resection of Colorectal Cancer

This trial is a randomized, double-blind, multinational Phase III study to evaluate the efficacy and safety of preemptive treatment with FTD/TPI compared with administration of placebo as follow-up, which is the standard of care, in patients who underwent curative resection of colorectal cancer and then tested positive for ctDNA.

Inclusion Criteria:

1. Patients who have been histopathologically diagnosed with colorectal adenocarcinoma

2. Patients who have undergone radical curative resection of the primary and metastatic tumors

3. Patients with colon or rectal cancer of Stage III based on final findings (T any N1/2 M0) (UICC TNM Classification, 8th Edition) who have a past history of standard postoperative chemotherapy

4. Patients who tested positive for ctDNA using SignateraTM by an analysis of the latest blood samples collected within 3 months prior to enrollment

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

6. Patients who are capable of oral ingestion

7. Patients aged 20 years or older at the time of informed consent

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

9. Patients who have no severe disorder in major organs (such as the bone marrow, heart, lungs, liver, and kidneys) and meet the following criteria (Data obtained most recently and within 14 days of the date of enrollment will be used for enrollment. Data obtained 2 weeks before the date of enrollment, on the same day of the week as the enrollment date, may be used for enrollment.)

   • 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

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

11. 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:

1. Patients with a history of treatment with FTD/TPI
2. Patients with a history of treatment with 2 or more regimens of postoperative adjuvant chemotherapy (Preoperative chemotherapy will not be counted as a regimen.)
3. Patients with a past history of a malignant tumor
4. Patients with a local or systemic active infection requiring intervention
5. Patients who are positive for HBs antigen or positive for HCV antibody
6. Patients who are positive for HIV antibody (Patients who have not been tested for HIV antibody may be enrolled.)
7. Patients with poorly controlled infections or diabetes
8. Patients with a past history of interstitial lung diseases (such as interstitial pneumonia and pulmonary fibrosis) requiring treatment or extensive findings of these diseases on CT
9. Patients with a serious complication
10. Patients who have been receiving systemic administration (oral or intravenous) of steroids (for 2 weeks or more at a dose of the equivalent of ≥ 10 mg/day of prednisolone)
11. Patients for whom enrollment in the trial is difficult because of clinically problematic psychiatric disorders
12. Pregnant or lactating women
13. Patients with reproductive potential who do not wish to use adequate contraceptive measures during the period of participation in the trial and during the contraception period
14. Patients who are judged by the attending physician to be ineligible for enrollment in the trial for other reasons