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.
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13 June 2017
In the version of this Review published online ahead of print, the details of the author contributions were missing. The author contributions arenow included in the HTML and PDF versions of the article.
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Acknowledgements
L.M. has received funding support from the Oak Foundation. The work of A.D.J.P. has been funded through a Cancer Research UK Life Chair and Programme Grant included within a Cancer Research UK ICR Core Award (C347/A15403), and is supported by the NIHR RM/ICR Biomedical Research Centre. C.M.Z. receives support from a KiKa-foundation (project 113) grant. We thank M. White (freelance editor and medical writer) for editorial support in the preparation of this article and G. Cook for administrative assistance. Editorial support costs have been funded by institutional funds from CNIO–HNJ Clinical Research Unit at Hospital Niño Jesus
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Moreno, L., Pearson, A., Paoletti, X. et al. Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective. Nat Rev Clin Oncol 14, 497–507 (2017). https://doi.org/10.1038/nrclinonc.2017.59
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