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A road map for designing phase I clinical trials of radiotherapy-novel agent combinations

Brown, Sarah R., Hinsley, Samantha, Hall, Emma, Hurt, Chris, Baird, Richard D., Forster, Martin, Scarsbrook, Andrew F. and Adams, Richard A. 2022. A road map for designing phase I clinical trials of radiotherapy-novel agent combinations. Clinical Cancer Research 10.1158/1078-0432.CCR-21-4087

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Radiotherapy has proven efficacy in a wide range of cancers. There is growing interest in evaluating radiotherapy–novel agent combinations and a drive to initiate this earlier in the clinical development of the novel agent, where the scientific rationale and preclinical evidence for a radiotherapy combination approach are high. Optimal design, delivery, and interpretation of studies are essential. In particular, the design of phase I studies to determine safety and dosing is critical to an efficient development strategy. There is significant interest in early-phase research among scientific and clinical communities over recent years, at a time when the scrutiny of the trial methodology has significantly increased. To enhance trial design, optimize safety, and promote efficient trial conduct, this position paper reviews the current phase I trial design landscape. Key design characteristics extracted from 37 methodology papers were used to define a road map and a design selection process for phase I radiotherapy–novel agent trials. Design selection is based on single- or dual-therapy dose escalation, dose-limiting toxicity categorization, maximum tolerated dose determination, subgroup evaluation, software availability, and design performance. Fifteen of the 37 designs were identified as being immediately accessible and relevant to radiotherapy–novel agent phase I trials. Applied examples of using the road map are presented. Developing these studies is intensive, highlighting the need for funding and statistical input early in the trial development to ensure appropriate design and implementation from the outset. The application of this road map will improve the design of phase I radiotherapy–novel agent combination trials, enabling a more efficient development pathway.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
Centre for Trials Research (CNTRR)
Additional Information: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .
Publisher: American Association for Cancer Research
ISSN: 1078-0432
Funders: CRUK
Date of First Compliant Deposit: 6 June 2022
Date of Acceptance: 28 April 2022
Last Modified: 06 Jun 2022 13:22

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