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

Colorectal Neoplasms Clinical Trial

— ALTAIR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04457297
• Other study ID #: EPOC 1905
• Secondary ID: JapicCTI-205363
• Status: Recruiting
• Phase: Phase 3
• Start date: July 8, 2020
• Est. completion date: December 2023

Study information

• Verified date: November 2022
• Source: National Cancer Center Hospital East
• Contact: Takayuki Yoshino, MD, PhD
• Phone: +81-4-7133-1111
• Email: prj-altair_core[@]eps.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Circulating Tumor DNA
• Colorectal Neoplasms
• Neoplasms
• Trifluridine and Tipiracil

Intervention

Drug:
• trifluridine and tipiracil
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.
• Placebo
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.

Locations

Country	Name	City	State
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyo	Tokyo
Japan	Chiba Cancer Center	Chiba
Japan	National Cancer Center Hospital	Chuo	Tokyo
Japan	Kyushu University Hospital	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Gifu University Hospital	Gifu
Japan	Kansai Medical University Hospital	Hirakata	Osaka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Shimane Prefectural Central Hospital	Izumo	Shimane
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital	Kawasaki	Kanagawa
Japan	Kagawa University Hospital	Kita	Kagawa
Japan	Hospital of the University of Occupational and Environmental Health	Kitakyushu	Fukuoka
Japan	Sano Hospital	Kobe	Hyogo
Japan	Cancer Institute Hospital Of JFCR	Koto	Tokyo
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kyoto-Katsura Hospital	Kyoto
Japan	University Hospital, Kyoto Prefectural Univercity of Medicine	Kyoto
Japan	Aizawa Hospital	Matsumoto	Nagano
Japan	Shikoku Cancer Center	Matsuyama	Ehime
Japan	Kyorin University Hospital	Mitaka	Tokyo
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	University of the Ryukyus Hospital	Nakagami	Okinawa
Japan	Okayama University Hospital	Okayama
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Tohoku University Hospital	Sendai	Miyagi
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Osaka University Hospital	Suita	Osaka
Japan	Osaka Medical and Pharmaceutical University Hospital	Takatsuki	Osaka
Japan	Toyama University Hospital	Toyama
Japan	University of Tsukuba Hospital	Tsukuba	Ibaraki
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Japan	Yokohama City University Medical Center	Yokohama	Kanagawa
Japan	University of Fukui Hospital	Yoshida	Fukui
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Center Hospital East	Alpha-A, Inc.

Countries where clinical trial is conducted

Japan,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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