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

Phase 3

Recruiting

• Conditions: Colorectal Neoplasms; Trifluridine and Tipiracil; Circulating Tumor DNA
• Interventions: Drug: trifluridine and tipiracil; Drug: Placebo

• Registration Number: NCT04457297
• Lead Sponsor: National Cancer Center Hospital East

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-25
• Study First Submitted QC: 2020-06-30
• Study First Posted: 2020-07-07
• Study Start: 2020-07-08
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-15
• Last Update Posted: 2022-11-18
• Primary Completion: 2023-05
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
trifluridine and tipiracil	trifluridine and tipiracil	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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, development of a secondary colorectal cancer lesion other than a relapse and death from any cause.

Secondary Outcome Measures

Name	Time	Method
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.
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.
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. 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.
Incidence of Adverse Events	Up to 3 years	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.
Treatment Completion Rate	Up to 3 years	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

Trial Locations

Locations (39)

Aichi Cancer Center Hospital; 🇯🇵 Nagoya, Aichi, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan

Shikoku Cancer Center; 🇯🇵 Matsuyama, Ehime, Japan

University of Fukui Hospital; 🇯🇵 Yoshida, Fukui, Japan

Hospital of the University of Occupational and Environmental Health; 🇯🇵 Kitakyushu, Fukuoka, Japan

Sapporo Medical University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Sano Hospital; 🇯🇵 Kobe, Hyogo, Japan

University of Tsukuba Hospital; 🇯🇵 Tsukuba, Ibaraki, Japan

Kanazawa University Hospital; 🇯🇵 Kanazawa, Ishikawa, Japan

Scroll for more (29 remaining)