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Novel Early Phase Clinical Trial Design in Oncology

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Abstract

The development of investigational medicinal products from pre-clinical package to product launch is a process that may be beset by pitfalls and expensive failures. The focus of this review is to provide an overview of how the conventional design of early phase oncology clinical trials has been modified with the advent of molecular profiling into treatment paradigms. We identify classical and alternative trial endpoints in an era of molecularly targeted agents and immunotherapy, and consider how personalised medicine has impacted on clinical trial design with reference to basket, umbrella and multi-arm expansion cohorts. Finally, we assess the impact of agile, adaptive and ‘intelligent’ trial design for patients, clinicians and trial centres, and how these challenges may be overcome to accelerate the approval of novel drugs for patient benefit.

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Abbreviations

IMP:

Investigational medicinal product

IT:

Immunotherapy

MTA:

Molecularly targeted agent

MTD:

Maximum tolerated dose

OBD:

Optimal biological dose

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Authors and Affiliations

  1. The Christie NHS Foundation Trust, Manchester, UK

    Ciara O’Brien, Louise Carter, Natalie Cook & Emma Dean

  2. The University of Manchester, Manchester, UK

    Natalie Cook & Emma Dean

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  1. Ciara O’Brien
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  2. Louise Carter
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Correspondence to Emma Dean.

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No funding assistance was provided for the work contained within this review article.

Conflict of interest

Drs O’Brien, Carter and Cook have no disclosures to declare. Dr Emma Dean has subsequently taken up employment with AstraZeneca. The Christie NHS Foundation Trust receives funding from the National Institute for Health Research and Experimental Cancer Medicine Centre, Grant award C1467/A15578.

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O’Brien, C., Carter, L., Cook, N. et al. Novel Early Phase Clinical Trial Design in Oncology. Pharm Med 31, 297–307 (2017). https://doi.org/10.1007/s40290-017-0205-7

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