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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colorectal Neoplasms, Trifluridine and Tipiracil, Circulating Tumor DNA

Intervention / Treatment
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* Drug: trifluridine and tipiracil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been histopathologically diagnosed with colorectal adenocarcinoma Patients who have undergone radical curative resection of the primary and metastatic tumors 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 Patients who tested positive for ctDNA using SignateraTM by an analysis of the latest blood samples collected within 3 months prior to enrollment Patients with no obvious relapse confirmed by chest, abdominal, and pelvic CT scans, etc. Patients who are capable of oral ingestion Patients aged 20 years or older at the time of informed consent 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 (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 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: Patients with a history of treatment with FTD/TPI Patients with a history of treatment with 2 or more regimens of postoperative adjuvant chemotherapy (Preoperative chemotherapy will not be counted as a regimen.) Patients with a past history of a malignant tumor Patients with a local or systemic active infection requiring intervention Patients who are positive for HBs antigen or positive for HCV antibody Patients who are positive for HIV antibody (Patients who have not been tested for HIV antibody may be enrolled.) Patients with poorly controlled infections or diabetes 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 Patients with a serious complication 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) Patients for whom enrollment in the trial is difficult because of clinically problematic psychiatric disorders Pregnant or lactating women 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 Patients who are judged by the attending physician to be ineligible for enrollment in the trial for other reasons

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: trifluridine and tipiracil<br> | Drug: trifluridine and tipiracil<br>* Trifluridine and tipiracil will be orally administered twice daily on Days 1 to 5 and Days 8 to 12. The administration will be repeated until completion of 6 courses(one course consists of 28 days) or until any discontinuation criterion is met.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo will be orally administered twice daily on Days 1 to 5 and Days 8 to 12. The administration will be repeated until completion of 6 courses(one course consists of 28 days) or until any discontinuation criterion is met.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival 1 (DFS1) | The time from the date of enrollment to any of the following events, whichever occurs first: a relapse, development of a secondary colorectal cancer lesion other than a relapse and death from any cause. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Conversion to Negative ctDNA | This rate is defined as the proportion of subjects who became negative for ctDNA at the test immediately after completion of study treatment. | Up to 2 years | 
| Disease-free survival 2 (DFS2) | The time from the date of enrollment to any of the following events, whichever occurs first: a relapse, development of a cancer lesion other than a relapse (secondary cancer), and death from any cause. In surviving subjects who have not been judged to have a relapse, the last date of survival with confirmation of no relapse be treated as the end of this period. | Up to 3 years | 
| Overall Survival (OS) | The time from the date of enrollment to the date of death from any cause. In surviving subjects, the last date of confirmation of survival will be treated as the end of this period. In subjects lost to follow-up, the last date of confirmation of survival before loss to follow-up will be treated as the end of this period. | Up to 3 years | 
| Incidence of Adverse Events | For each of the AEs due to the following study treatment, the frequency of cases with the worst grade in all courses according to CTCAE v5.0 will be calculated using all treated patients as the denominator. | Up to 3 years | 
| Treatment Completion Rate | This rate will be calculated for each eligible subject in accordance with the following equation. Treatment completion rate (%) = number of treatment courses completed/6 × 100 | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Neoplasms, Gastrointestinal Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Antineoplastic Agents, trifluridine and tipiracil