Clinical Trials List
Protocol NumberEP0C1905
NCT Number(ClinicalTrials.gov Identfier)NCT04457297
2020-06-16 - 2023-12-31
Phase III
Recruiting1
ICD-9153.9
Malignant neoplasm of colon, unspecified
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
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Trial Applicant
EPS International Holdings Co., Ltd.
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Sponsor
National Cancer Center Hospital East(NCCHE)
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Trial scale
Multi-Regional Multi-Center
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Update
2023/03/10
Investigators and Locations
Co-Principal Investigator
- 陳國興 Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
- 郭弘揚 Division of General Surgery
- 賴碩倫 未分科
- 廖斌志 Division of Hematology & Oncology
- TSUNG-HAO LIU Division of General Surgery
- 陳姿君 未分科
- YU-YUN SHAO Division of Hematology & Oncology
- 呂理駿 Division of General Surgery
- 黃約翰 未分科
- 梁逸歆 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- JHE-CYUAN GUO Division of General Surgery
- 洪基翔 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Curative Resection of colorectal cancer
Objectives
This trial will be conducted in patients who underwent curative resection of colorectal cancer and then tested positive in monitoring using SignateraTM, a system by Natera, Inc. for detecting blood circulating tumor DNA (ctDNA) for the detection of residual tumor, with no apparent relapse on imaging. The objective of the trial is to verify the efficacy and safety of preemptive treatment with trifluridine/tipiracil hydrochloride (FTD/TPI) compared with followup, which is the standard of care.
Test Drug
LONSURF
Active Ingredient
Trifluridine, Tipiracil hydrochloride
Dosage Form
film-coated tablet
film-coated tablet
film-coated tablet
Dosage
15
20
20
Endpoints
Primary endpoint:
Disease-free survival 1*1*3 (DFS1)
*1 In this trial, a DFS1 event is defined as a relapse, development of a
secondary large intestine carcinoma lesion other than a relapse (an
intramucosal cancer lesion will not be treated as an event), and death.
Secondary endpoints：
Rate of conversion to negative ctDNA
Disease-free survival 2*2*3 (DFS2)
Overall survival*3 (OS)
Incidence of adverse events
Treatment completion rate
QOL
*2 In this trial, a DFS2 event is defined as a relapse, development of a
cancer lesion other than a relapse (secondary cancer), and death.
*3 After the end of the trial period, subjects will be followed up for 5 years
in a separate observational study
Disease-free survival 1*1*3 (DFS1)
*1 In this trial, a DFS1 event is defined as a relapse, development of a
secondary large intestine carcinoma lesion other than a relapse (an
intramucosal cancer lesion will not be treated as an event), and death.
Secondary endpoints：
Rate of conversion to negative ctDNA
Disease-free survival 2*2*3 (DFS2)
Overall survival*3 (OS)
Incidence of adverse events
Treatment completion rate
QOL
*2 In this trial, a DFS2 event is defined as a relapse, development of a
cancer lesion other than a relapse (secondary cancer), and death.
*3 After the end of the trial period, subjects will be followed up for 5 years
in a separate observational study
Inclution Criteria
Inclusion criteria:
1. Patients who have been histopathologically diagnosed with
colorectal adenocarcinoma
2. Patients who have undergone radical resection*1 of the primary
and metastatic tumors
*1 It is considered to be a radical resection if the tumor is
exposed at the edge or on the surface of surgical detachment
but is encapsulated.
3. Patients with colon cancer of Stage III based on final findings
(T any N1*2/2 M0) (UICC TNM Classification, 8th Edition) who
have a past history of standard postoperative chemotherapy*3
*2 N1c (UICC TNM Classification, 8th Edition) is also included
in this stage (tumor deposits, or satellite nodules, are seen in
the adjacent soft tissues of the colon or rectum without
subserosal layer or peritoneal coat, with no regional lymph
node metastasis).
*3 Treatments described in the current Japanese and overseas
guidelines or study treatments conducted in clinical studies.
4. Patients who tested positive for ctDNA using SignateraTM by
an analysis*4 of the latest blood samples collected within 3
months prior to enrollment
*4 Analyses of blood samples using SignateraTM will be
performed in a separate clinical study (see Section 2.10.1.2.).
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
1. Patients who have been histopathologically diagnosed with
colorectal adenocarcinoma
2. Patients who have undergone radical resection*1 of the primary
and metastatic tumors
*1 It is considered to be a radical resection if the tumor is
exposed at the edge or on the surface of surgical detachment
but is encapsulated.
3. Patients with colon cancer of Stage III based on final findings
(T any N1*2/2 M0) (UICC TNM Classification, 8th Edition) who
have a past history of standard postoperative chemotherapy*3
*2 N1c (UICC TNM Classification, 8th Edition) is also included
in this stage (tumor deposits, or satellite nodules, are seen in
the adjacent soft tissues of the colon or rectum without
subserosal layer or peritoneal coat, with no regional lymph
node metastasis).
*3 Treatments described in the current Japanese and overseas
guidelines or study treatments conducted in clinical studies.
4. Patients who tested positive for ctDNA using SignateraTM by
an analysis*4 of the latest blood samples collected within 3
months prior to enrollment
*4 Analyses of blood samples using SignateraTM will be
performed in a separate clinical study (see Section 2.10.1.2.).
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
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*5 (Preoperative
chemotherapy will not be counted as a regimen.)
*5 The timing of initiation of the postoperative adjuvant
chemotherapy will not be specified.
3. Patients with a past history of a malignant tumor*6
*6 Patients with a relapse-free survival period of 5 years or
longer, or patients with basal cell or squamous cell carcinoma
of the skin that is considered cured by local treatment,
superficial bladder cancer, cervical cancer, carcinoma in situ
(intraepithelial cancer) or lesions equivalent to intramucosal
cancer, or non-metastatic prostate cancer not requiring
systemic treatment may be enrolled.
4. Patients with a local or systemic active infection requiring
intervention
5. Patients who are positive for HBs antigen or positive for HCV
antibody*7
*7 Patients who are positive for HCV antibody but negative for
HCV-RNA may be enrolled.
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*8
*8 Gastrointestinal hemorrhage, heart disease, glaucoma, etc.
10. Patients who have been receiving continuous 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
(see “4.3 Pregnancy and Contraception”)
14. Patients who are judged by the attending physician to be
ineligible for enrollment in the trial for other reasons
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*5 (Preoperative
chemotherapy will not be counted as a regimen.)
*5 The timing of initiation of the postoperative adjuvant
chemotherapy will not be specified.
3. Patients with a past history of a malignant tumor*6
*6 Patients with a relapse-free survival period of 5 years or
longer, or patients with basal cell or squamous cell carcinoma
of the skin that is considered cured by local treatment,
superficial bladder cancer, cervical cancer, carcinoma in situ
(intraepithelial cancer) or lesions equivalent to intramucosal
cancer, or non-metastatic prostate cancer not requiring
systemic treatment may be enrolled.
4. Patients with a local or systemic active infection requiring
intervention
5. Patients who are positive for HBs antigen or positive for HCV
antibody*7
*7 Patients who are positive for HCV antibody but negative for
HCV-RNA may be enrolled.
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*8
*8 Gastrointestinal hemorrhage, heart disease, glaucoma, etc.
10. Patients who have been receiving continuous 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
(see “4.3 Pregnancy and Contraception”)
14. Patients who are judged by the attending physician to be
ineligible for enrollment in the trial for other reasons
The Estimated Number of Participants
-
Taiwan
5 participants
-
Global
240 participants
