Clinical trial NCT04457297: Initial Attack on Latent Metastasis Using TAS-102 for ct DNA Identified Colorectal Cancer Patients After Curative Resection
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colorectal Neoplasms
Trifluridine and Tipiracil
Circulating Tumor DNA
Keywords: Colorectal Neoplasms
Gastrointestinal Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Antineoplastic Agents
trifluridine and tipiracil
Lead sponsor: National Cancer Center Hospital East
Sponsor class: OTHER
Collaborators: name: Alpha-A, Inc.
First posted: 2020-07-07
Enrollment: 240
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Disease-free survival 1 (DFS1)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Rate of Conversion to Negative ctDNA
timeFrame: Up to 2 years
measure: Disease-free survival 2 (DFS2)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Incidence of Adverse Events
timeFrame: Up to 3 years
measure: Treatment Completion Rate
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: Shikoku Cancer Center
state: Ehime
city: Yoshida
country: Japan
facility: University of Fukui Hospital
state: Fukui
city: Kitakyushu
country: Japan
facility: Hospital of the University of Occupational and Environmental Health
state: Fukuoka
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Sano Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Kita
country: Japan
facility: Kagawa University Hospital
state: Kagawa
city: Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Matsumoto
country: Japan
facility: Aizawa Hospital
state: Nagano
city: Nakagami
country: Japan
facility: University of the Ryukyus Hospital
state: Okinawa
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Takatsuki
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
state: Osaka
city: Izumo
country: Japan
facility: Shimane Prefectural Central Hospital
state: Shimane
city: Bunkyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
state: Tokyo
city: Chuo
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto
country: Japan
facility: Cancer Institute Hospital Of JFCR
state: Tokyo
city: Mitaka
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural Univercity of Medicine
city: Kyoto
country: Japan
facility: Kyoto-Katsura Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: