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Clinical Trial
. 2023 Aug 5;23(1):726.
doi: 10.1186/s12885-023-11199-1.

Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G)

Naoki Takahashi  1 , Hiroki Hara  2 , Kengo Nagashima  3 , Kenro Hirata  4 , Toshiki Masuishi  5 , Toshihiko Matsumoto  6 , Hisato Kawakami  7 , Kentaro Yamazaki  8 , Shuichi Hironaka  9 , Narikazu Boku  10 , Kei Muro  5
Affiliations
Clinical Trial

Randomised phase II trial of trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM) versus trifluridine/tipiracil for previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma (RETRIEVE study, WJOG15822G)

Naoki Takahashi et al. BMC Cancer. .

Abstract

Background: Trifluridine/tipiracil (FTD/TPI) prolongs survival in the third- or later-line treatment for advanced gastric cancer (GC), esophagogastric junction (EGJ) adenocarcinoma, and colorectal cancer. While single-arm phase II trials showed promising outcomes of FTD/TPI plus ramucirumab (RAM) as third- or later-line treatments for advanced GC or EGJ cancer, there have been no clinical trials to directly compare FTD/TPI plus RAM with FTD/TPI monotherapy. Therefore, we have started a randomised phase II trial to evaluate the efficacy and safety of FTD/TPI plus RAM compared with FTD/TPI monotherapy as third- or later-line treatments in patients with advanced GC and EGJ adenocarcinoma.

Methods: This RETREVE trial (WJOG15822G) is a prospective, open-label, randomised, multicentre phase II trial comparing FTD/TPI plus RAM versus FTD/TPI monotherapy in a third- or later-line setting. Eligibility criteria include age of > 20 years; performance status of 0 or 1; unresectable or recurrent gastric or EGJ adenocarcinoma; confirmed HER2 status; refractory or intolerant to fluoropyrimidine, taxane or irinotecan; refractory to RAM (not intolerant); and at least a measurable lesion per RECIST 1.1. FTD/TPI (35 mg/m2 twice daily, evening of day 1 to morning of day 6 and evening of day 8 to morning of day 13) was administered orally every 4 weeks, and RAM (8 mg/kg) was administered intravenously every 2 weeks. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival, objective response rate, disease control rate, and safety. The expected hazard ratio of PFS is set as 0.7, assuming 4-month PFS rate of 27% in FTD/TPI monotherapy and 40% in FTD/TPI plus RAM. The number of subjects was 110, with a one-sided alpha error of 0.10 and power of 0.70.

Discussion: This study will clarify the additional effect of RAM continuation beyond disease progression on FTD/TPI in the third- or later-line setting for patients with advanced GC or EGJ cancer.

Trial registration: jRCTs041220120.

Keywords: Angiogenesis inhibitor; Esophagogastric Junction adenocarcinoma; Gastric cancer; Ramucirumab; Trifluridine/tipiracil.

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Conflict of interest statement

NT has received honoraria from Taiho. HH has received honoraria form Eli Lilly and Taiho, and research grant from Taiho. KN has received a consulting fee (paid to the university) from Eli Lilly. KH has received research grant from Taiho. TM (Toshiki Masuishi) have no conflicts of interest to declare. TM (Toshihiko Matsumoto) has received honoraria from Eli Lilly and Taiho. HK has received consulting fees from Eli Lilly and Taiho, and research funding from Taiho. KY has received research grant from Taiho, and received honoraria from Taiho and Eli Lilly. SH has received honoraria from Eli Lilly and Taiho. NB has received honoraria from Eli Lilly and Taiho. KM has received research grant from Taiho, and received honoraria from Taiho and Eli Lilly.

Figures

Fig. 1
Fig. 1
Study schema of RETRIEVE study
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