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Background <p>Screening failure, loss of eligibility after trial consent and before the initial administration of an investigational new drug (IND), can delay the development of anticancer agents in Phase I trials. However, the previous literature on characteristics of these patients has been limited. Consequently, this study aimed to identify the factors associated with screening failure in this modern era of early drug development.</p> Methods <p>This retrospective, observational study included data from all patients referred to a Phase I trial centre at the Japanese Foundation for Cancer Research, Tokyo, Japan, from August 2020 to May 2023. Referral patient data were collected from electronic medical records and analysed.</p> Results <p>Of the 331 patients referred, 73 were excluded primarily due to slot unavailability and 84 did not meet the inclusion criteria. The remaining 174 patients gave a trial consent: 31 failed screening; 3 dropped out after the initial administration of an IND; 4 were during the first cycle of an IND; and 136 completed the first cycle or discontinued due to dose-limiting toxicities (DLTs). Screening failure was primarily attributable to disease progression during the screening period (45.2%), followed by infectious diseases, transaminitis, and incompatible gene polymorphisms (9.7% each). Age, sex, and cancer type were similar between the patients who failed screening compared with those who completed the first cycle or discontinued due to DLTs. Between these patient groups, statistically significant differences were observed in baseline brain metastasis (<i>p</i> = 0.0044) and ascites (<i>p</i> = 0.015) on Fisher's exact test, in performance status (PS) (<i>p</i> = 0.036) on Mann–Whitney U test, and in albumin levels (<i>p</i> = 0.013) and the number of days from referral to trial consent (<i>p</i> = 0.027) on Student's <i>t</i>-test. Additionally, brain metastasis, ascites and PS ≥ 1 were associated with disease progression during the screening period.</p> Conclusion <p>Phase I trial candidates presenting with brain metastases, ascites, decreased albumin levels, and PS ≥ 1 at baseline should be carefully evaluated, as these factors are associated with an increased risk of screening failure primarily due to disease progression during the screening period.</p>

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Patient characteristics related to screening failure in Phase I trials

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月4日

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  • Haruka Ozaki,
  • Eriko Miyawaki,
  • Naoki Miyazaki,
  • Masahiro Kuno,
  • Kana Kurokawa,
  • Ippei Miyamoto,
  • Yohei Arihara,
  • Shota Fukuoka,
  • Yukinori Ozaki,
  • Makiko Ono,
  • Masato Ozaka,
  • Mayu Yunokawa,
  • Shunji Takahashi,
  • Takayuki Ueno,
  • Takahiro Kogawa,
  • Shigehisa Kitano

摘要

Background

Screening failure, loss of eligibility after trial consent and before the initial administration of an investigational new drug (IND), can delay the development of anticancer agents in Phase I trials. However, the previous literature on characteristics of these patients has been limited. Consequently, this study aimed to identify the factors associated with screening failure in this modern era of early drug development.

Methods

This retrospective, observational study included data from all patients referred to a Phase I trial centre at the Japanese Foundation for Cancer Research, Tokyo, Japan, from August 2020 to May 2023. Referral patient data were collected from electronic medical records and analysed.

Results

Of the 331 patients referred, 73 were excluded primarily due to slot unavailability and 84 did not meet the inclusion criteria. The remaining 174 patients gave a trial consent: 31 failed screening; 3 dropped out after the initial administration of an IND; 4 were during the first cycle of an IND; and 136 completed the first cycle or discontinued due to dose-limiting toxicities (DLTs). Screening failure was primarily attributable to disease progression during the screening period (45.2%), followed by infectious diseases, transaminitis, and incompatible gene polymorphisms (9.7% each). Age, sex, and cancer type were similar between the patients who failed screening compared with those who completed the first cycle or discontinued due to DLTs. Between these patient groups, statistically significant differences were observed in baseline brain metastasis (p = 0.0044) and ascites (p = 0.015) on Fisher's exact test, in performance status (PS) (p = 0.036) on Mann–Whitney U test, and in albumin levels (p = 0.013) and the number of days from referral to trial consent (p = 0.027) on Student's t-test. Additionally, brain metastasis, ascites and PS ≥ 1 were associated with disease progression during the screening period.

Conclusion

Phase I trial candidates presenting with brain metastases, ascites, decreased albumin levels, and PS ≥ 1 at baseline should be carefully evaluated, as these factors are associated with an increased risk of screening failure primarily due to disease progression during the screening period.