がん分子標的薬の長期毒性データに基づく新規ベイズ流用量探索デザインの研究開発

• Project/Area Number: 17K00045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Statistical science
• Research Institution: The University of Tokyo
• Principal Investigator: 平川 晃弘 東京大学, 大学院医学系研究科(医学部), 特任准教授 (90609330)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Granted (Fiscal Year 2019)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん臨床試験 / 用量探索デザイン / ベイズ流デザイン / バスケットデザイン / 分子標的薬 / ベイズ統計学 / 用量探索法 / アダプティブデザイン

Outline of Annual Research Achievements

分子標的薬のためのLassoを用いた用量探索法を開発し論文投稿を行った。長期毒性データを考慮する用量探索法といて、Relative dose intensity (RDI)に基づく漸減・漸増デザインを開発し論文投稿を行った。
また、がん早期探索試験の領域においてマスタープロトコル試験の概念が提唱され、これに伴いバスケット型臨床試験デザインの研究開発が増加している。本研究課題においても、これまでの成果を活用してバスケットデザインの研究開発に取り組んだ。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

がん分子標的薬の長期毒性データを考慮した用量探索法を包括的に研究し論文投稿すると共に、米国National Cancer Institute (NCI)との共同研究も実施し当該領域に新たな研究成果をもたらした。また、新たな研究課題としてバスケットデザインの研究開発も行い、論文を投稿している。

Strategy for Future Research Activity

がんゲノム医療のためのバスケット型臨床デザインの研究開発を進める。

Research Products

• [Int'l Joint Research] National Cancer Institute(米国)
• [Int'l Joint Research] National Cancer Institute(米国)
• [Int'l Joint Research]
• [Journal Article] A dose-finding approach for genomic patterns in phase I trials. (2020)
  • Author(s): Kaneko S, Hirakawa A, Kakurai Y, Hamada C.
  • Journal Title: Journal of Biopharmaceutical Statistics Volume: -
  • DOI: 10.1080/10543406.2020.1744619
  • Peer Reviewed
• [Journal Article] Pragmatic dose-escalation methods incorporating relative dose intensity assessment for molecularly targeted agents in phase I trials. (2019)
  • Author(s): Hirakawa A, Tanaka Y, Kaneko S.
  • Journal Title: Contemporary Clinical Trial Communications Volume: 16
  • DOI: 10.1016/j.conctc.2019.100489
  • Peer Reviewed / Open Access
• [Journal Article] A comparative study of longitudinal toxicities of cytotoxic drugs, molecularly targeted agents, immunomodulatory drugs, and cancer vaccines (2019)
  • Author(s): Hirakawa A, Sudo K, Yonemori K, Sadachi R, Kinoshita F, Kobayashi Y, Okuma SH, Kawachi A, Tamura K, Fujiwara Y, Rubinstein L, Takebe N.
  • Journal Title: Clinical Pharmacology & Therapeutics Volume: 106 Pages: 803-809
  • DOI: 10.1002/cpt.1442
  • Peer Reviewed
• [Journal Article] がん臨床試験におけるベイズ流バスケットデザインの理論と実装 (2019)
  • Author(s): 平川晃弘，浅野淳一，佐藤宏征，橋本大哉，手良向聡
  • Journal Title: 計量生物学 Volume: 39 Pages: 103-122
  • NAID: 130007644700
  • Peer Reviewed
• [Journal Article] マスタープロトコルに基づくがん臨床試験 (2019)
  • Author(s): 平川晃弘，浅野淳一，佐藤宏征，手良向聡
  • Journal Title: 計量生物学 Volume: 39 Pages: 85-101
  • NAID: 130007644694
  • Peer Reviewed
• [Journal Article] Dose individualization and variable selection using Bayesian Lasso in early phase dose-finding trials (2019)
  • Author(s): Kakurai Y, Kaneko S, Hamada C, Hirakawa A
  • Journal Title: Applied Statistics Volume: 68 Pages: 445-460
  • DOI: 10.1111/rssc.12326
  • Peer Reviewed
• [Journal Article] Master protocol trials in oncology: Review and new trial designs (2018)
  • Author(s): 33.Hirakawa A, Asano J, Sato H, Teramukai S
  • Journal Title: Contemporary Clinical Trials Communications Volume: 12 Pages: 1-8
  • DOI: 10.1016/j.conctc.2018.08.009
  • Peer Reviewed / Open Access
• [Journal Article] Potential utility of a longitudinal relative dose intensity of molecularly targeted agents in phase 1 dose-finding trial. (2018)
  • Author(s): Hirakawa A, Yonemori K, Kinoshita F, Kobayashi Y, Okuma H. Kawachi A, Tamura K, Fujiwara Y, Rubinstein L, Harris PJ, Takebe N.
  • Journal Title: Cancer Science Volume: 1 Pages: 207-214
  • DOI: 10.1111/cas.13436
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Dose-Finding Method for Molecularly Targeted Agents Incorporating the Relative Dose Intensity in Phase I Oncology Clinical Trials. (2019)
  • Author(s): Tanaka Y, Sozu T, Hirakawa A
  • Organizer: ENAR 2019 Spring Meeting
  • Int'l Joint Research
• [Presentation] Heterogeneity Assessment of Treatment Effect among Subpopulations in Basket Trials (2019)
  • Author(s): Sadachi R, Hirakawa A
  • Organizer: ENAR 2019 Spring Meeting
  • Int'l Joint Research
• [Presentation] A Basket Trial Design using Bayesian Model Averaging. (2019)
  • Author(s): Hirakawa A, Sadachi R
  • Organizer: ENAR 2019 Spring Meeting
  • Int'l Joint Research
• [Presentation] A clustering-based basket design (2019)
  • Author(s): Hirakawa A
  • Organizer: 3rd Pacific Rim Cancer Biostatistics Workshop
  • Int'l Joint Research
• [Presentation] Utility of Bayesian single-arm design in new drug application for rare cancers in Japan: application to basket trial data (2019)
  • Author(s): Hirakawa A
  • Organizer: 6th International Society of Biopharmaceutical Statistics
  • Int'l Joint Research
• [Book] Modern Dose-Finding Designs for Cancer Phase I Trials: Drug Combinations and Molecularly Targeted Agents (2018)
  • Author(s): Hirakawa, A., Sato, H., Daimon, T., Matsui, S.
  • Total Pages: 104
  • Publisher: Springer
  • ISBN: 9784431555728