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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms; Circulating Tumor DNA; Trifluridine and Tipiracil
• Intervention / Treatment: Drug: trifluridine and tipiracil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Takayuki Yoshino, MD, PhD; Phone Number: +81-4-7133-1111; Email: prj-altair_core@eps.co.jp

Study Locations

• Japan
  • Chiba, Japan, 260-8717
    • Recruiting
    • Chiba Cancer Center
    • Principal Investigator: Tadamichi Denda, Dr.
  • Fukuoka, Japan, 812-8582
    • Recruiting
    • Kyushu University Hospital
    • Principal Investigator: Eiji Oki, Dr.
  • Fukuoka, Japan, 811-1395
    • Recruiting
    • National Hospital Organization Kyushu Cancer Center
    • Principal Investigator: Masaru Morita, Dr.
  • Gifu, Japan, 501-1194
    • Recruiting
    • Gifu University Hospital
    • Principal Investigator: Nobuhisa Matsuhashi, Dr.
  • Hiroshima, Japan, 734-8551
    • Recruiting
    • Hiroshima University Hospital
    • Principal Investigator: Hideki Ohdan, Dr.
  • Kumamoto, Japan, 860-8556
    • Recruiting
    • Kumamoto University Hospital
    • Principal Investigator: Yuji Miyamoto, Dr.
  • Kyoto, Japan, 602-8566
    • Recruiting
    • University Hospital, Kyoto Prefectural Univercity of Medicine
    • Principal Investigator: Yoshiaki Kuriu, Dr.
  • Kyoto, Japan, 615-8256
    • Recruiting
    • Kyoto-Katsura Hospital
    • Principal Investigator: Dai Manaka, Dr.
  • Okayama, Japan, 700-8558
    • Recruiting
    • Okayama University Hospital
    • Principal Investigator: Fuminori Teraishi, Dr.
  • Osaka, Japan, 540-0006
    • Recruiting
    • National Hospital Organization Osaka National Hospital
    • Principal Investigator: Takeshi Kato, Dr.
  • Saitama, Japan, 362-0806
    • Recruiting
    • Saitama Cancer Center
    • Principal Investigator: Hiroki Hara, Dr.
  • Shizuoka, Japan, 411-8777
    • Recruiting
    • Shizuoka Cancer Center
    • Principal Investigator: Kentaro Yamazaki, Dr.
  • Toyama, Japan, 930-0194
    • Recruiting
    • Toyama University Hospital
    • Principal Investigator: Shinya Kajiura, Dr.
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center Hospital
      • Principal Investigator: Toshiki Masuishi, Dr.
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
      • Principal Investigator: Yoshiaki Nakamura, Dr.
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • Recruiting
      • Shikoku Cancer Center
      • Principal Investigator: Tomohiro Nishina, Dr.
  • Fukui
    • Yoshida, Fukui, Japan, 910-1193
      • Recruiting
      • University of Fukui Hospital
      • Principal Investigator: Takanori Goi, Dr.
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 807-8556
      • Recruiting
      • Hospital of the University of Occupational and Environmental Health
      • Principal Investigator: Keiji Hirata, Dr.
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Recruiting
      • Hokkaido University Hospital
      • Principal Investigator: Yoshito Komatsu, Dr.
    • Sapporo, Hokkaido, Japan, 060-8543
      • Recruiting
      • Sapporo Medical University Hospital
      • Principal Investigator: Ichiro Takemasa, Dr.
  • Hyogo
    • Kobe, Hyogo, Japan, 655-0031
      • Recruiting
      • Sano Hospital
      • Principal Investigator: Masahito Kotaka, Dr.
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • Recruiting
      • University of Tsukuba Hospital
      • Principal Investigator: Toshikazu Moriwaki, Dr.
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
      • Recruiting
      • Kanazawa University Hospital
      • Principal Investigator: Keishi Nakamura, Dr.
  • Kagawa
    • Kita, Kagawa, Japan, 761-0793
      • Recruiting
      • Kagawa University Hospital
      • Principal Investigator: Akihito Tsuji, Dr.
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • Recruiting
      • St. Marianna University School of Medicine Hospital
      • Principal Investigator: Yu Sunakawa, Dr.
    • Yokohama, Kanagawa, Japan, 232-0024
      • Recruiting
      • Yokohama City University Medical Center
      • Principal Investigator: Jun Watanabe, Dr.
    • Yokohama, Kanagawa, Japan, 241-8515
      • Recruiting
      • Kanagawa Cancer Center
      • Principal Investigator: Manabu Shiozawa, Dr.
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Recruiting
      • Tohoku University Hospital
      • Principal Investigator: Masanobu Takahashi, Dr.
  • Nagano
    • Matsumoto, Nagano, Japan, 390-8510
      • Recruiting
      • Aizawa Hospital
      • Principal Investigator: Masato Nakamura, Dr.
  • Okinawa
    • Nakagami, Okinawa, Japan, 903-0215
      • Recruiting
      • University of the Ryukyus Hospital
      • Principal Investigator: Mitsuhisa Takatsuki, Dr.
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Recruiting
      • Kansai Medical University Hospital
      • Principal Investigator: Shogen Boku, Dr.
    • Suita, Osaka, Japan, 565-0871
      • Recruiting
      • Osaka University Hospital
      • Principal Investigator: Mamoru Uemura, Dr.
    • Takatsuki, Osaka, Japan, 569-8686
      • Recruiting
      • Osaka Medical and Pharmaceutical University Hospital
      • Principal Investigator: Masahiro Gotou, Dr.
  • Shimane
    • Izumo, Shimane, Japan, 693-8555
      • Recruiting
      • Shimane Prefectural Central Hospital
      • Principal Investigator: Akiyoshi Kanazawa, Dr.
  • Tokyo
    • Bunkyo, Tokyo, Japan, 113-8677
      • Recruiting
      • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
      • Principal Investigator: Kazushige Kawai, Dr.
    • Chuo, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
      • Principal Investigator: Atsuo Takashima, Dr.
    • Koto, Tokyo, Japan, 135-8550
      • Recruiting
      • Cancer Institute Hospital of JFCR
      • Principal Investigator: Kensei Yamaguchi, Dr.
    • Mitaka, Tokyo, Japan, 181-8611
      • Recruiting
      • Kyorin University Hospital
      • Principal Investigator: Eiji Sunami
• Taiwan
  • Taipei, Taiwan, 100229
    • Recruiting
    • National Taiwan University Hospital
    • Principal Investigator: Kun-Huei Yeh, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: 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.
Experimental: trifluridine and tipiracil	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: National Cancer Center Hospital East
• Collaborators: Alpha-A, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 25, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Gastrointestinal Diseases; Digestive System Diseases; Antineoplastic Agents; Colorectal Neoplasms; Gastrointestinal Neoplasms; trifluridine and tipiracil
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Trifluridine
• Other Study ID Numbers: EPOC 1905; JapicCTI-205363 (Registry Identifier: Japic Clinical Trials Information)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No