Clinical Trial Protocol

Phase II biomarker identification study of anti-VEGF agents with FOLFIRI for pretreated metastatic colorectal cancer

https://orcid.org/0000-0003-3759-1214

Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

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Satoshi Otsu

*Author for correspondence: Tel.: +81 97 586 6275;

E-mail Address: ootu@oita-u.ac.jp

Department of Medical Oncology & Hematology, Oita University Faculty of Medicine, Yufu, Japan

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Shuichi Hironaka

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan

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Atsuo Takashima

Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

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Junki Mizusawa

Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

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Tomoko Kataoka

Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

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Haruhiko Fukuda

Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan

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Shunsuke Tsukamoto

Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan

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Tetsuya Hamaguchi

Department of Gastroenterological Oncology, Saitama Medical University International Medical Center, Saitama, Japan

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Yukihide Kanemitsu

Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan

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Published Online:16 Aug 2023https://doi.org/10.2217/fon-2023-0097

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Abstract

Chemotherapy plus antiangiogenic agents, including bevacizumab, ramucirumab and aflibercept, is a standard second-line treatment for patients with metastatic colorectal cancer, but which specific agents should be selected is ambiguous due to a lack of clear evidence from prospective studies. Previous reports have suggested ramucirumab and aflibercept could be more effective than bevacizumab in patients with high VEGF-D and high VEGF-A, respectively. JCOG2004 is a three-arm, randomized, phase II study to identify predictive biomarkers for these agents in patients who have failed first-line treatment. The study will enroll 345 patients from 52 institutions for 2 years, with progression-free survival in high VEGF-D (bevacizumab vs ramucirumab) and high VEGF-A (bevacizumab vs aflibercept) serving as the primary end point.

Clinical Trial Registration:jRCTs031220058 (www.jrct.niph.go.jp)

Tweetable abstract

A multi-institutional randomized phase II study to identify predictive biomarkers for antiangiogenic agents with FOLFIRI in second-line treatment of patients with metastatic colorectal cancer was started in May 2022.

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Papers of special note have been highlighted as: • of interest

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Vol. 19, No. 23

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History

Received 5 February 2023

Accepted 12 July 2023

Published online 16 August 2023

Published in print July 2023

Information

Keywords

Author contributions

All authors were involved in the conceptualization of this study. J Mizusawa and H Fukuda were responsible for data curation. S Otsu, S Hironaka, A Takashima, T Kataoka, T Hashimoto, J Mizusawa and H Fukuda conducted the formal analysis, applying statistical or mathematical techniques to analyze the data. S Otsu, S Hironaka, Y Kanemitsu and H Fukuda were involved in funding acquisition. J Mizusawa and H Fukuda developed the methodology, designing the methods and procedures used in the research. T Hashimoto, T Kataoka, J Mizusawa and H Fukuda managed the project administration and provided key resources. H Fukuda was responsible for the software. S Otsu, S Hironaka, Y Kanemitsu and H Fukuda provided supervision, overseeing the research team and ensuring the research was conducted appropriately. T Hashimoto, S Otsu and S Hironaka drafted the original manuscript. All authors reviewed and edited the paper and approved the submitted version.

Acknowledgments

The authors are grateful to all patients registered, investigators and G&G Science Co. Ltd for their cooperation in JCOG2004. The authors appreciate proofreading of the English language performed by San Francisco Edit (http://www.sfedit.net).

Financial & competing interests disclosure

This study is supported by the National Cancer Center Research and Development Fund (2020-J-3, 2023-J-03). The costs required for biomarker evaluations are funded by G&G Science Co., Ltd, Japan. T Hamaguchi reports honoraria from Lilly and Chugai Pharmaceutical outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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