A road map for designing phase I clinical trials of radiotherapy–novel agent combinations
A road map for designing phase I clinical trials of radiotherapy–novel agent combinations
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.
3639-3651
Brown, Sarah R.
514dd72b-5b0d-4254-9ac6-fb88d705ce62
Hinsley, Samantha
acf114b5-f5c2-4e61-ba74-73570fe16aaa
Hall, Emma
c0b0a284-935e-468d-80d2-a30c067ed0b3
Hurt, Chris
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
2 September 2022
Brown, Sarah R.
514dd72b-5b0d-4254-9ac6-fb88d705ce62
Hinsley, Samantha
acf114b5-f5c2-4e61-ba74-73570fe16aaa
Hall, Emma
c0b0a284-935e-468d-80d2-a30c067ed0b3
Hurt, Chris
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Brown, Sarah R., Hinsley, Samantha and Hall, Emma
,
et al.
(2022)
A road map for designing phase I clinical trials of radiotherapy–novel agent combinations.
Clinical Cancer Research, 28 (17), .
(doi:10.1158/1078-0432.CCR-21-4087).
Abstract
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.
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Accepted/In Press date: 30 April 2022
Published date: 2 September 2022
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Local EPrints ID: 488109
URI: http://eprints.soton.ac.uk/id/eprint/488109
ISSN: 1078-0432
PURE UUID: c9c87914-d346-4606-a247-01699a5028d1
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Date deposited: 15 Mar 2024 17:47
Last modified: 23 Mar 2024 03:13
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Author:
Sarah R. Brown
Author:
Samantha Hinsley
Author:
Emma Hall
Author:
Chris Hurt
Corporate Author: et al.
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