臨床研究等提出・公開システム

Phase2 study of intrapatient dose-escalation of biweekly trifluridine/tipiracil + bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (E-BiTS study)

E-BiTS study

36

Median age of 65, male with 47%, ECOG PS1 with 22%, colon cancer with 75%, differentiated adenocarcinoma with 100%, number of metastatic organs >=2 with 81%, liber metastasis with 67%, RAS wild type with 42%, primary tumor resected with 67%

Patients registered to this study from 7 institutions between 1st November 2022 and 28th December 2023. Two patients did not meet inclusion criteria after registration, and Full analysis set (FAS) was 34. After protocol treatment was initiated, one patient changed hospital before first CT image, and Per Protocol Set (PPS) was 33.

Leukopenia (Any grade/ Grade >=3) 68%/18% Neutropenia (Any grade/ Grade >=3) 74%/24% Anemia (Any grade/ Grade >=3) 76%/21% Thrombocytopenia (Any grade/ Grade>=3) 29%/0% Proteinuria (Any grade/ Grade >=3) 38%/6% Hemorrhage (Any grade/ Grade >=3) 24%/3%, Intestinal perforation (Any grade/ Grade >=3) 3%/3%, Nausea (Any grade/ Grade>=3) 38%/0%, Vomiting (Any grade/ Grade >=3) 29%/0%, Diarrhea (Any grade/ Grade >=3) 38%/0%, Mucositis (Any grade/ Grade >=3) 24%/0%, Febrile neutropenia (Any grade/ Grade>=3) 0%/0%, Treatment related severe adverse events 9%, There was one case each of gastrointestinal perforation, renal infection, and gastrointestinal bleeding. Treatment related death 0%

The DCR was 72.7% (80% confidence interval: 60.4-82.8). The PFS was 5.6 months (95% confidence interval: 2.7-6.5). The OS was 17.6 months (95% confidence interval: 10.1-NA). The rate of dose escalation of FTD/TPI was 91%. The relative dose intensity of FTD/TPI during whole protocol treatment was 110.6%.

E-BiTS study achieved its primary endpoint, DCR. Our study suggests that intrapatient dose-escalation of FTD/TPI might be effective for patients treated by bi-weekly FTD/TPI+BEV with acceptable adverse events.

May. 31, 2025

Aug. 28, 2025

https://doi.org/10.1016/j.esmoop.2025.105571

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs041220085

Taniguchi Hiroya

Aichi Cancer Center Hospital

1-1,Kanokoden,Chikusa-ku,Nagoya,Aichi

hiroya.taniguchi@aichi-cc.jp

Wakabayashi Munehiro

Toho University Omori Medical Center

6-11-1,Omorinishi,Ota-ku,Tokyo

+81-3-3762-4151

munehiro.wakabayashi@med.toho-u.ac.jp

Complete

Nov. 01, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Patients has been diagnosed with unresectable advanced or recurrent colorectal adenocarcinoma by histopathological diagnosis.
2) The age of patients on registration date is 20 years or older.
3) ECOG PS 0 or 1.
4) Patients have measurable lesions.
5) Patients have a history of refractory or intolerant to the following chemotherapy.
(1) All three drugs, fluorinated pyrimidine anticancer drug, oxaliplatin, and irinotecan
(2) Angiogenesis inhibitor (bevacizumab, ramucirumab, or aflibercept)
(3) Anti-EGFR antibody drug (cetuximab or panitumumab) in RAS wild type
(4) BRAF inhibitor (encorafenib) in BRAF mutant
(5) Immune checkpoint inhibitors (pembrolizumabor nivolumab) in MSI-H
6) Patients who have not been treated with FTD/TPI.
7) Patients who can take orally
8) Patients are expected to live for 3 months or longer
9) Patients whose latest test values within 14 days before registration meet all of the following.
(1) Number of neutrophils >= 1500/mm3
(2) Platelet count >= 75000/mm3
(3) Total bilirubin <= 1.5 mg / dL
(4) AST <= 100 U/L
(5) ALT <= 100 U/L
(6) Serum creatinine <= 1.5 mg/dL and Ccr >= 60mL/min
(7) Urine protein (test paper method) 1+ or less, or UPC (Urine Protein Creatinine) ratio <= 2.0
10) Patients have given written consent to participate in the study.

1) Patients with double cancers requiring chemotherapy (excluding hormone therapy)
2) Patients have infectious diseases which need systemic treatment.
3) Patients have difficulty in being enrolled in this study due to clinically problematic mental illness
4) Patients with the following complications
(1) Renal failure
(2) Cirrhosis / liver failure
(3) Chronic lung disease requiring oxygen administration
(4) Concomitant with unstable angina (angina whose onset or seizures have worsened within the last 3 weeks) or a history of myocardial infarction within 6 months
(5) Other complications that the doctor in charge considers to be serious
5) Patients receiving continuous systemic administration of steroids or immunosuppressants
6) Patients with unstable thromboembolism.
7) Pregnant women, lactating women, women who may be pregnant now, or patients who are not willing to use contraception
8) Patients judged by the investigator to be inappropriate

Both

colorectal cancer

Patients will receive biweekly FTD/TPI (35mg twice daily on days 1-5, every 2 weeks) with BEV (5mg/kg on day 1, every 2weeks).Between second cycles and fourth cycles, the dose of FTD/TPI will be escalated if patients meet criteria of FTD/TPI dose escalation.

Disease control rate

Overall survival: OS
Progression free survival: PFS
Response rate: RR
Relative Dose Intensity: RDI
Increase implementation rate
Adverse effect (AE) occurrence rate

+81-52-762-6111

Oct. 06, 2022

none