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)

BMC Cancer · 11 authors, 9 centres

AI SUMMARY

FIDELITY 100%

POPULATIONPreviously treated patients with advanced gastric or esophagogastric junction adenocarcinoma

INTERVENTIONTrifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM)

COMPARISONTrifluridine/tipiracil (FTD/TPI) monotherapy

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

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TL;DR

This is a protocol for a randomised phase II trial comparing the combination of trifluridine/tipiracil plus ramucirumab against trifluridine/tipiracil monotherapy in patients with previously treated advanced gastric or esophagogastric junction adenocarcinoma. The study plans to evaluate progression-free survival as the primary endpoint.

Full summary

984 CHARS

This document presents the protocol for the RETRIEVE trial (WJOG15822G), a randomised phase II study. The trial is designed to compare the efficacy and safety of FTD/TPI plus RAM versus FTD/TPI monotherapy as a third- or later-line treatment for advanced gastric or esophagogastric junction adenocarcinoma. The primary endpoint is progression-free survival, with overall survival, objective response rate, disease control rate, and safety as secondary endpoints. The study aims to randomise 110 subjects with a one-sided alpha error of 0.10 and power of 0.70, assuming an expected hazard ratio for PFS of 0.7. The discussion contextualises the trial by reviewing evidence for anti-angiogenic therapies in gastric and colorectal cancers, including preclinical models and clinical data for similar combinations. It highlights the rationale for evaluating FTD/TPI plus RAM, particularly given its potential synergy with prior anti-PD-1 therapy and emerging data on later-line treatments.

PICO

PPOPULATION

Previously treated patients with advanced gastric or esophagogastric junction adenocarcinoma

IINTERVENTION

Trifluridine/tipiracil (FTD/TPI) plus ramucirumab (RAM)

OOUTCOME

Progression-free survival (primary), overall survival, objective response rate, disease control rate, and safety (secondary)

STUDY TYPE

other

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10403909

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)

BMC Cancer

READ THE FULL PAPER

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/m 2 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. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-11199-1.

CITATION EXPORT

Naoki Takahashi, Hiroki Hara, Kengo Nagashima et al.. 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). BMC Cancer. (2023). https://doi.org/10.1186/s12885-023-11199-1

AUTHORS

11 · 9 CENTRES

Naoki Takahashi, Hiroki Hara, Kengo Nagashima, Kenro Hirata, Toshiki Masuishi, Toshihiko Matsumoto, Hisato Kawakami, Kentaro Yamazaki, Shuichi Hironaka, Narikazu Boku, Kei Muro

1https://ror.org/03a4d7t12grid.416695.90000 0000 8855 274XDepartment of Gastroenterology, Saitama Cancer Center, 780 Komuro, Ina-Machi, Kita-Adachi-Gun, Saitama, 362-0807 Japan
2https://ror.org/01k8ej563grid.412096.80000 0001 0633 2119Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, 35 Shinanomachi, Tokyo, 160-8582 Japan
3https://ror.org/02kn6nx58grid.26091.3c0000 0004 1936 9959Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582 Japan
4https://ror.org/03kfmm080grid.410800.d0000 0001 0722 8444Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-Ku Nagoya 464-8681, Aichi, Japan
5https://ror.org/001xjdh50grid.410783.90000 0001 2172 5041Cancer Treatment Center, Kansai Medical University, 2-3-1 Hirakatashinmachi, Hirakata, Osaka, 573-1191 Japan
6https://ror.org/05kt9ap64grid.258622.90000 0004 1936 9967Department of Medical Oncology, Faculty of Medicine, Kindai University, Osakasayama, Osaka, 589-8511 Japan
7https://ror.org/0042ytd14grid.415797.90000 0004 1774 9501Department of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777 Japan
8https://ror.org/0188yz413grid.411205.30000 0000 9340 2869Department of Medical Oncology, Faculty of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611 Japan
9grid.26999.3d0000 0001 2151 536XDepartment of Oncology and General Medicine, IMSUT Hospital, Institute of Medical Science, University of Tokyo, 4-6-1 Shiroganedai, Minato-Ku, Tokyo, 108-8639 Japan