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Phase I trial of intravenous Ad5CRT in patients with liver metastasis of gastrointestinal cancers

Cancer Gene Therapy volume 26, pages 174–178 (2019)Cite this article

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Abstract

We conducted a phase 1 trial for single-dose intravenous Ad5CRT, a replication-defective adenovirus vector expressing HSVtk (herpes simplex virus thymidine kinase) modulated by a specific trans-splicing ribozyme that targets human telomerase reverse transcriptase (hTERT)-encoding RNAs. Dose-limiting toxicities (DLTs) were evaluated in 15 patients at dose levels of 0.1–2 × 1012 virus particles. Patients well tolerated study treatment. During the DLT evaluation period, none of the 15 patients developed any grade 4 toxicities or treatment discontinuation that was related to agents investigated by this trial. The most frequent treatment-related adverse event was fever/chill (26.7%). Of the 18 patients, no patients achieved a partial or complete response, and the median progression-free survival for 18 patients was 1.1 months (95% CI, 1.0–1.3) and the results suggest no clinical benefit from this treatment. Ad5CRT’s circulating virus half-life was approximately 10 min. Maximum tolerated dose was 2 × 1012 virus particles. Single-dose intravenous Ad5CRT was feasible and well tolerated in patients with gastrointestinal cancer liver metastasis. Ad5CRT did not provide meaningful clinical benefit, and the reason for the lack of efficacy was not entirely clear because no pharmocodynamic assessment was made.

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Funding

This study was supported by National Cancer Center grants (NCC-1610281 and 1810950).

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Authors and Affiliations

  1. National Cancer Center, Goyang, Gyeonggi, 10408, Republic of Korea

    Sang-Jin Lee, Seung-Pil Shin, Seung Hee Lee, Jeong Won Kang, Myeong-Cherl Kook, In-Hoo Kim & Hark Kyun Kim

  2. National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Gyeonggi, 10408, Republic of Korea

    In-Hoo Kim & Hark Kyun Kim

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  1. Sang-Jin Lee
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Correspondence to Hark Kyun Kim.

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Lee, SJ., Shin, SP., Lee, S.H. et al. Phase I trial of intravenous Ad5CRT in patients with liver metastasis of gastrointestinal cancers. Cancer Gene Ther 26, 174–178 (2019). https://doi.org/10.1038/s41417-018-0055-9

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