Circulating Tumor DNA, Colorectal Neoplasms, Trifluridine and Tipiracil
Conditions
Keywords
Colorectal Neoplasms, Gastrointestinal Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Antineoplastic Agents, trifluridine and tipiracil
Brief summary
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.
Interventions
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.
DRUGPlacebo
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.
Sponsors
National Cancer Center Hospital East
Alpha-A, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival 1 (DFS1) | Up to 3 years | The time from the date of enrollment to any of the following events, whichever occurs first: a relapse, the first development of a secondary colorectal cancer lesion other than a relapse and death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Conversion to Negative ctDNA | Up to 2 years | This rate is defined as the proportion of subjects who became negative for ctDNA at the test immediately after completion of study treatment. |
| Disease-free Survival 2 (DFS2) | Up to 3 years | 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. For survives with no evidence of recurrence, DFS2 data will be censored at the last imaging date of confirmed no recurrence. Subjects for which no imaging have been performed, DFS2 data will be censored at the date of enrollment. |
| Overall Survival (OS) | Up to 3 years | 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. |
| Treatment Completion Rate | Up to 3 years | This rate had calculated for each eligible subject in accordance with the following equation: Treatment completion rate (%) = number of treatment courses completed/6 × 100 |
| QOL (Week 24 Only) | Up to 1 year | Measure Description: Quality of Life was assessed using two validated instruments: EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) evaluates cancer-specific HRQoL across domains: Global Health Status/QoL (range: 0-100, higher = better global health/QoL), Functional Scales (Physical, Role, Emotional, Cognitive, Social; each range: 0-100, higher = better functioning), Symptom Scales (Fatigue, Nausea/vomiting, Pain, Dyspnoea, Insomnia, Appetite loss, Constipation, Diarrhoea, Financial difficulties): each 0-100 (higher = worse/more severe symptoms). Scores are linearly transformed; subscales are reported individually (not summed). EQ-5D-5L (EuroQOL 5-Dimension 5-Level) measures general health across five dimensions: Index Score (range: -1.000 to 1.000, higher = better health), Visual Analogue Scale (VAS) (range: 0-100, higher = better health). Unit of Measure: scores on a scale. Note: Only Week 24 results are presented. |
Countries
Japan, Taiwan
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 134 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants |
| Age, Continuous | 67.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 121 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 121 participants |
| Region of Enrollment Taiwan | 0 participants |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 122 | 0 / 121 |
| other Total, other adverse events | 120 / 122 | 69 / 121 |
| serious Total, serious adverse events | 6 / 122 | 0 / 121 |
Outcome results
None listed