Early phase clinical trials of anticancer agents in children and adolescents-an ITCC perspective

Lucas Moreno, Andrew D.J. Pearson, Xavier Paoletti, Irene Jimenez, Birgit Geoerger, Pamela R. Kearns, C. Michel Zwaan, Francois Doz, Andre Baruchel, Josef Vormoor, Michela Casanova, Stefan M. Pfister, Bruce Morland, Gilles Vassal

Research output: Contribution to journalReview article

Abstract

In the past decade, the landscape of drug development in oncology has evolved dramatically; however, this paradigm shift remains to be adopted in early phase clinical trial designs for studies of molecularly targeted agents and immunotherapeutic agents in paediatric malignancies. In drug development, prioritization of drugs on the basis of knowledge of tumour biology, molecular 'drivers' of disease and a drug's mechanism of action, and therapeutic unmet needs are key elements; these aspects are relevant to early phase paediatric trials, in which molecular profiling is strongly encouraged. Herein, we describe the strategy of the Innovative Therapies for Children with Cancer (ITCC) Consortium, which advocates for the adoption of trial designs that enable uninterrupted patient recruitment, the extrapolation from studies in adults when possible, and the inclusion of expansion cohorts. If a drug has neither serious dose-related toxicities nor a narrow therapeutic index, then studies should generally be started at the adult recommended phase II dose corrected for body surface area, and act as dose-confirmation studies. The use of adaptive trial designs will enable drugs with promising activity to progress rapidly to randomized studies and, therefore, will substantially accelerate drug development for children and adolescents with cancer.

Original languageEnglish
Pages (from-to)497-507
Number of pages11
JournalNature Reviews Clinical Oncology
Volume14
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

ASJC Scopus subject areas

  • Oncology

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    Moreno, L., Pearson, A. D. J., Paoletti, X., Jimenez, I., Geoerger, B., Kearns, P. R., Zwaan, C. M., Doz, F., Baruchel, A., Vormoor, J., Casanova, M., Pfister, S. M., Morland, B., & Vassal, G. (2017). Early phase clinical trials of anticancer agents in children and adolescents-an ITCC perspective. Nature Reviews Clinical Oncology, 14(8), 497-507. https://doi.org/10.1038/nrclinonc.2017.59