Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report

Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period. In this paper we describe how we modified the design of the RAMPART trial (NCT03288532) which was set up to investigate immune checkpoint inhibitor therapy in the adjuvant renal cancer setting. The trial had been initiated when no globally accepted adjuvant strategy after nephrectomy existed. A subsequent change in the standard of care for many patients with early renal cancer meant it was no longer feasible to continue to recruit. We needed to find a way to maximise the contribution that RAMPART participants could make to the evidence base for immune checkpoint inhibitor therapy without introducing bias or detriment to the integrity of the trial results. We describe how we agreed and incorporated all design and timeline changes while remaining blinded to accumulating data within the trial, thus protecting the reliability of the future results. We share details of our design modifications to guide others who may have similar experiences, particularly as more agents and combinations of agents are developed and investigated in similar adjuvant settings.

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Publication Details

Journal
Contemporary Clinical Trials Communications
Published
2024-10-18
DOI
https://doi.org/10.1016/j.conctc.2024.101381
Primary Topic
Statistical Methods in Clinical Trials
Type
article
Field-Weighted Citation Impact
0.00

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article

Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report

Jay Patel, T. Powles, Jemima Thompson, Mahesh Parmar et al.
Contemporary Clinical Trials Communications
Statistical Methods in Clinical Trials
article

Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report

Jay Patel, T. Powles, Jemima Thompson, Mahesh Parmar, Clare Shakeshaft, Tim Eisen, Grisma Patel, Alison Fielding, Babak Choodari‐Oskooei, Salena Mulhere, Toni K. Choueiri, Richard Kaplan, Angela Meade, Martin R. Stockler, Ian D. Davis, David J. Harrison, Axel Bex, Laurence Albigès, James Larkin, Nat Thorogood, Grant Duncan Stewart, Cristina Suárez, Hannah L. Rush, Craig Gedye, Paul Nathan, Eleni Frangou, Balaji Venugopal, A.W.S. Ritchie, Hannah Plant
article en

Abstract

Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period. In this paper we describe how we modified the design of the RAMPART trial (NCT03288532) which was set up to investigate immune checkpoint inhibitor therapy in the adjuvant renal cancer setting. The trial had been initiated when no globally accepted adjuvant strategy after nephrectomy existed. A subsequent change in the standard of care for many patients with early renal cancer meant it was no longer feasible to continue to recruit. We needed to find a way to maximise the contribution that RAMPART participants could make to the evidence base for immune checkpoint inhibitor therapy without introducing bias or detriment to the integrity of the trial results. We describe how we agreed and incorporated all design and timeline changes while remaining blinded to accumulating data within the trial, thus protecting the reliability of the future results. We share details of our design modifications to guide others who may have similar experiences, particularly as more agents and combinations of agents are developed and investigated in similar adjuvant settings.

Contemporary Clinical Trials CommunicationsVol. 42
Hebron University (PS), The University of Sydney (AU), St Bartholomew's Hospital (GB), Royal Marsden NHS Foundation Trust (GB), University of St Andrews (GB), Royal Free London NHS Foundation Trust (GB), University of Cambridge (GB), Institut Gustave Roussy (FR), Cambridge University Hospitals NHS Foundation Trust (GB), The Netherlands Cancer Institute (NL), MRC Clinical Trials Unit at UCL (GB), Bridge University (SS), Eastern Health (AU), Mount Vernon Cancer Centre (GB), Oncode Institute (NL), Dana-Farber Cancer Institute (US), Royal Marsden Hospital (GB), Vall d'Hebron Hospital Universitari (ES), Cancer Research UK Scotland Institute (GB), Australian and New Zealand Urogenital and Prostate Cancer Trials Group (AU), National Health and Medical Research Council (AU), University College London (GB), University of Newcastle Australia (AU)
AstraZeneca, Cancer Research UK, Kidney Cancer UK, Medical Research Council, National Health and Medical Research Council
Peace, Justice and strong institutions
Openalex Percentile: Top 81%
Statistical Methods in Clinical Trials
DOIOpen Access PDFOpenAlex
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