ALTAIR study

JRCT ID: jRCT2080225267

Registered date:07/07/2020

Basic Information

• Recruitment status: completed
• Health condition(s) or Problem(s) studied: Colorectal cancer
• Date of first enrollment: 21/07/2020
• Target sample size: 240
• Countries of recruitment: Japan,Asia except Japan
• Study type: Interventional

Intervention(s)

investigational material(s)
Generic name etc : Lonsurf combination tablet T15/T20
INN of investigational material : trifluridine + tipiracil hydrochloride
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : In 1 course consisting of 28 days, FTD/TPI or placebo will be orally administered twice daily after breakfast and after dinner for 5 consecutive days (Days 1 to 5 and Days 8 to 12), followed by withdrawal for 2 days. After repeating this cycle twice, the subject is withdrawn from study treatment for 14 days.

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : In 1 course consisting of 28 days, FTD/TPI or placebo will be orally administered twice daily after breakfast and after dinner for 5 consecutive days (Days 1 to 5 and Days 8 to 12), followed by withdrawal for 2 days. After repeating this cycle twice, the subject is withdrawn from study treatment for 14 days.

Outcome(s)

Primary Outcome

Efficacy
Disease-Free Survival 1 (DFS1) The time from the date of enrollment to any of the following events, whichever occurs first: a relapse, the first development of a secondary large intestine carcinoma lesion other than a relapse (an intramucosal cancer lesion will not be treated as an event) that is confirmed after the date of enrollment, and death from any cause. For survives with no evidence of recurrence, DFS1 data will be censored at the last imaging date of confirmed no recurrence. Subjects for which no imaging have been performed, DFS1 data will be censored at the date of enrollment. In principle, events will be assessed by the investigator.

Secondary Outcome

efficacy
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.
efficacy
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. For survives with no evidence of recurrence, DFS2 data will be censored at the last imaging date of confirmed no recurrence. Subjects for which no imaging have been performed, DFS2 data will be censored at the date of enrollment. In principle, events will be assessed by the investigator.
efficacy
Overall Survival (OS)
Definition of 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 (the confirmation may be performed by telephone, and the fact of confirmation shall be recorded in the medical records.) 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.
safety
Incidence of Adverse Events
For each of the adverse events 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.
efficacy
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
safety
QOL
QOL will be assessed using EORTC QLQ C-30 and EQ-5D-5L.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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 or rectal 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 4 5
*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 When preoperative chemotherapy or preoperative chemoradiotherapy was performed for rectal cancer of stage III (T any N1 * 2/2 M0) (UICC TNM Classification, 8th Edition), it does not matter if standard chemotherapy is performed or not.
*4 Treatments described in the current Japanese and overseas guidelines or study treatments conducted in clinical studies
*5 In case of patients who do not have a standard
postoperative chemotherapy for rational reason, these patients can be enrolled.
Note that if sites enroll such patients, record the reason
for the decision to medical chart.
4.Patients who tested positive for ctDNA using SignateraTM by an analysis*6 of the latest blood samples collected within 3 months prior to enrollment.
*6 Analyses of blood samples using SignateraTM will be performed in a separate clinical study
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

Exclude 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.)
*7 The timing of initiation of the postoperative adjuvant chemotherapy will not be specified.
3.Patients with a past history of a malignant tumor*6
*8 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*9 or positive for HCV antibody*10
*9 HBV-DNA testing is mandatory to be below the limit of detection for patients with a negative HBs antigen test, but with a positive test result for either HBs antibody or HBc antibody
*10 Patients who are positive for HCV antibody but negative for HCV-RNA may be enrolled.
6.Patients who are positive for HIV antibody *11(Patients who have not been tested for HIV antibody may be enrolled.)
*11 Patients who are positive for HIV antibody but negative for HIV-RNA 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
*12 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
14.Patients who are judged by the attending physician to be ineligible for enrollment in the trial for other reasons.

Related Information

• Primary Sponsor: Yoshino Takayuki
• Secondary Sponsor: -
• Source(s) of Monetary Support: TAIHO PHARMACEUTICAL CO., LTD.,Alpha-A, Inc.
• Secondary ID(s): NCT04457297,JapicCTI-205363