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 p...

Full description

Saved in:
Bibliographic Details
Main Authors: Angela Meade, Elena Frangou, Babak Choodari-Oskooei, James Larkin, Tom Powles, Grant D. Stewart, Laurence Albiges, Axel Bex, Toni K. Choueiri, Ian D. Davis, Tim Eisen, Alison Fielding, Craig Gedye, David J. Harrison, Rick Kaplan, Salena Mulhere, Paul Nathan, Grisma Patel, Jay Patel, Hannah Plant, Alastair Ritchie, Hannah Rush, Clare Shakeshaft, Martin R. Stockler, Cristina Suarez, Jemima Thompson, Nat Thorogood, Balaji Venugopal, Mahesh K.B. Parmar
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Contemporary Clinical Trials Communications
Online Access:http://www.sciencedirect.com/science/article/pii/S2451865424001285
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846117774657585152
author Angela Meade
Elena Frangou
Babak Choodari-Oskooei
James Larkin
Tom Powles
Grant D. Stewart
Laurence Albiges
Axel Bex
Toni K. Choueiri
Ian D. Davis
Tim Eisen
Alison Fielding
Craig Gedye
David J. Harrison
Rick Kaplan
Salena Mulhere
Paul Nathan
Grisma Patel
Jay Patel
Hannah Plant
Alastair Ritchie
Hannah Rush
Clare Shakeshaft
Martin R. Stockler
Cristina Suarez
Jemima Thompson
Nat Thorogood
Balaji Venugopal
Mahesh K.B. Parmar
author_facet Angela Meade
Elena Frangou
Babak Choodari-Oskooei
James Larkin
Tom Powles
Grant D. Stewart
Laurence Albiges
Axel Bex
Toni K. Choueiri
Ian D. Davis
Tim Eisen
Alison Fielding
Craig Gedye
David J. Harrison
Rick Kaplan
Salena Mulhere
Paul Nathan
Grisma Patel
Jay Patel
Hannah Plant
Alastair Ritchie
Hannah Rush
Clare Shakeshaft
Martin R. Stockler
Cristina Suarez
Jemima Thompson
Nat Thorogood
Balaji Venugopal
Mahesh K.B. Parmar
author_sort Angela Meade
collection DOAJ
description 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.
format Article
id doaj-art-152a532dd63f4c618fd32817ead311e1
institution Kabale University
issn 2451-8654
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series Contemporary Clinical Trials Communications
spelling doaj-art-152a532dd63f4c618fd32817ead311e12024-12-18T08:49:55ZengElsevierContemporary Clinical Trials Communications2451-86542024-12-0142101381Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and reportAngela Meade0Elena Frangou1Babak Choodari-Oskooei2James Larkin3Tom Powles4Grant D. Stewart5Laurence Albiges6Axel Bex7Toni K. Choueiri8Ian D. Davis9Tim Eisen10Alison Fielding11Craig Gedye12David J. Harrison13Rick Kaplan14Salena Mulhere15Paul Nathan16Grisma Patel17Jay Patel18Hannah Plant19Alastair Ritchie20Hannah Rush21Clare Shakeshaft22Martin R. Stockler23Cristina Suarez24Jemima Thompson25Nat Thorogood26Balaji Venugopal27Mahesh K.B. Parmar28MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UK; Corresponding author. Medical Research Council, Clinical Trials Unit at University College London, 90 High Holborn, London, WC1V 6LJ, UK.MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKRoyal Marsden Hospital, Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, UKSt Bartholomew's Hospital, W Smithfield, London, EC1A 7B, UKUniversity of Cambridge, Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UKInstitut Gustave Roussy, 114 Rue Edouard Vaillant 94805, Villejuif, FranceRoyal Free London NHS Foundation Trust UCL Division of Surgery and Interventional Science, Pond Street, London, NW3 2QG, UK; Netherlands Cancer Institute, Amsterdam, the NetherlandsDana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, United StatesMonash University Eastern Health Clinical School, Level 2, 5 Arnold Street, Box Hill, Victoria, 3128, Australia; Department of Medical Oncology, Eastern Health, Melbourne, AustraliaDepartment of Oncology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge Biomedical Campus, Hill's Road Cambridge, CB2 0QQ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKFaculty of Health and Medicine, The University of Newcastle, AustraliaUniversity of St Andrews, North Haugh, St Andrews, KY16 9TF, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMount Vernon Cancer Centre, Rickmansworth Rd, Northwood, HA6 2RN, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKNHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, 2006, Australia; ANZUP Cancer Trials Group, Sydney, AustraliaVall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, 08035, Barcelona, SpainMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKSchool of Cancer Sciences, Beatson Institute, University of Glasgow, G61 1BD, UKMRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London, WC1V 6LJ, UKClinical 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.http://www.sciencedirect.com/science/article/pii/S2451865424001285
spellingShingle Angela Meade
Elena Frangou
Babak Choodari-Oskooei
James Larkin
Tom Powles
Grant D. Stewart
Laurence Albiges
Axel Bex
Toni K. Choueiri
Ian D. Davis
Tim Eisen
Alison Fielding
Craig Gedye
David J. Harrison
Rick Kaplan
Salena Mulhere
Paul Nathan
Grisma Patel
Jay Patel
Hannah Plant
Alastair Ritchie
Hannah Rush
Clare Shakeshaft
Martin R. Stockler
Cristina Suarez
Jemima Thompson
Nat Thorogood
Balaji Venugopal
Mahesh K.B. Parmar
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
Contemporary Clinical Trials Communications
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://www.sciencedirect.com/science/article/pii/S2451865424001285
work_keys_str_mv AT angelameade adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT elenafrangou adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT babakchoodarioskooei adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT jameslarkin adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT tompowles adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT grantdstewart adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT laurencealbiges adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT axelbex adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT tonikchoueiri adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT ianddavis adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT timeisen adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT alisonfielding adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT craiggedye adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT davidjharrison adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT rickkaplan adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT salenamulhere adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT paulnathan adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT grismapatel adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT jaypatel adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT hannahplant adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT alastairritchie adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT hannahrush adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT clareshakeshaft adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT martinrstockler adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT cristinasuarez adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT jemimathompson adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT natthorogood adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT balajivenugopal adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport
AT maheshkbparmar adaptingthedesignoftheongoingramparttrialinresponsetoexternalevidenceanexamplefortrialswhichtakemanyyearstorunandreport