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. 2024 Feb;86(1):43-51.
doi: 10.18999/nagjms.86.1.43.

Protocol of a phase II study investigating the efficacy and safety of trifluridine/tipiracil plus ramucirumab as a third-line or later treatment for advanced gastric cancer

Koki Nakanishi  1 , Chie Tanaka  1 , Mitsuro Kanda  1 , Kazushi Miyata  2 , Nozomu Machida  3 , Mitsuru Sakai  4 , Daisuke Kobayashi  5 , Hitoshi Teramoto  6 , Akiharu Ishiyama  7 , Bin Sato  8 , Takashi Oshima  9 , Masaki Kajikawa  10 , Hidenobu Matsushita  11 , Kiyoshi Ishigure  12 , Katsuya Yamashita  13 , Shinichi Fujitake  14 , Satoshi Sueoka  4 , Takahiro Asada  10 , Dai Shimizu  1 , Shizuki Sugita  2 , Yachiyo Kuwatsuka  15 , Osamu Maeda  16 , Satoshi Furune  16 , Kenta Murotani  17 , Yuichi Ando  16 , Tomoki Ebata  2 , Yasuhiro Kodera  1
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Protocol of a phase II study investigating the efficacy and safety of trifluridine/tipiracil plus ramucirumab as a third-line or later treatment for advanced gastric cancer

Koki Nakanishi et al. Nagoya J Med Sci. 2024 Feb.

Abstract

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

Keywords: clinical trial; gastric cancer; ramucirumab; trifluridine tipiracil.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships that may be considered potential competing interests: Dr Nakanishi reports personal fees from Taiho Pharmaceutical Co, Ltd, Ono Pharmaceutical Co, Ltd, and Daiichi Sankyo Company, Ltd, outside the scope of the submitted work. Dr Kodera reports grants and personal fees from Taiho Pharmaceutical Co, Ltd, Chugai Pharma, MSD, Nihon Kayaku, Yakult, Lilly Japan, Ono Pharmaceutical Co, Ltd, Covidien, Daiichi Sankyo Company, Ltd, Tsumura, Johnson & Johnson, and Abbvie; grants from Takeda, Kaken Pharma, EA Pharma, Otsuka, Sanofi, Abbot, Bayer, and Pfizer; and personal fees from Miyarisan, Amgen, and Olympus, outside the scope of the submitted work. Dr Ando reports grants and personal fees from Chugai Pharmaceutical Co, Ltd, Kyowa Kirin Co, Ltd, Nippon Kayaku Co, Ltd, Yakult Honsha Co, Ltd, Ono Pharmaceutical Co, Ltd, Taiho Pharmaceutical Co, Ltd, Novartis Pharma KK, Daiichi Sankyo Company, Ltd, and Eisai Co, Ltd; personal fees from Eli Lilly Japan KK, Bayer Holding Ltd, Sawai Pharmaceutical Co, Ltd, MSD KK, Astellas Pharma Inc., Otsuka Holdings Co, Ltd, Sanwa Kagaku Kenkyusho Co, Ltd, Hisamitsu Pharmaceutical Co, Inc., SymBio Pharmaceuticals, Aptitude Health, and Alfresa Pharma Corporation; and grants from BeiGene, Ltd, outside the scope of the submitted work. Dr Murotani reports personal fees from Taiho Pharmaceutical Co, Ltd, outside the scope of the submitted work. The other authors declare that no financial or material support was received for this study.

Figures

Fig. 1
Fig. 1
Treatment protocol ECOG-PS: Eastern Cooperative Oncology Group performance score
Fig. 2
Fig. 2
Dosing schedule
Fig. 3
Fig. 3
Modified dosing schedule (Trifluridine tipiracil biweekly administration)
See this image and copyright information in PMC

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References

    1. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941–1953. doi:10.1002/ijc.31937. - DOI - PubMed
    1. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2021;24(1):1–21. doi:10.1007/s10120-020-01042-y. - DOI - PMC - PubMed
    1. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–697. doi:10.1016/S0140-6736(10)61121-X. - DOI - PubMed
    1. Kang YK, Chen LT, Ryu MH, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(2):234–247. doi:10.1016/S1470-2045(21)00692-6. - DOI - PubMed
    1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27–40. doi:10.1016/S0140-6736(21)00797-2. - DOI - PMC - PubMed

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