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Prostate cancer androgen receptor splice variant 7 biomarker study - A multicentre randomised feasibility trial of biomarker-guided personalised treatment in patients with advanced prostate cancer (the VARIANT trial) study protocol

Prostate cancer androgen receptor splice variant 7 biomarker study - A multicentre randomised feasibility trial of biomarker-guided personalised treatment in patients with advanced prostate cancer (the VARIANT trial) study protocol
Prostate cancer androgen receptor splice variant 7 biomarker study - A multicentre randomised feasibility trial of biomarker-guided personalised treatment in patients with advanced prostate cancer (the VARIANT trial) study protocol

Introduction Prostate cancer is the most common male cancer with one in four developing non-curable metastatic disease. Initial treatment responses to hormonal therapies are transient and further management options lie between (1) further hormone therapy or (2) a non-hormonal approach involving additional chemotherapy or molecular radiotherapy (radium-223). There is no clear rationale for choosing between these mechanistically different treatment approaches. The biology of hormone resistance is driven through abnormal androgen receptor activity and we can assay this through a blood test measuring androgen receptor variant 7 (AR-V7) expression in circulating tumour cells. Despite increasing evidence supporting AR-V7's role as a prognostic marker, the clinical utility of such measures remains unknown in helping personalise treatment decisions. Methods and design The VARIANT feasibility trial is a pragmatic design, to be run over 18 months with participants randomised into the intervention arm receiving biomarker (AR-V7) guided clinical treatment and participants randomised into the control arm with conventional standard management (no biomarker guidance). AR-V7 positive participants (likely to be insensitive to further hormone treatment) will receive chemotherapy or in other cases radium-223 (where routinely available). Seventy male ≥18 years old participants with metastatic castrate resistant prostate cancer clinically indicated to proceed to further hormone therapy or chemotherapy, will be recruited from three National Health Service Trusts based in England, Scotland and Wales. The feasibility primary outcome is willingness of patients to be randomised and clinicians to recruit to a biomarker-based treatment strategy, with trial data informing the basis of a definitive and appropriately powered randomised control trial. Ethics and dissemination Formal ethics review was undertaken with a favourable opinion, through Wales NRES Committee 2 18/WA/0419. Findings to be disseminated through patient and professional organisations that have expressed their support, media outlets and peer-reviewed journal publication. Trial registration number ISRCTN10246848; pre-results

adult oncology, cell biology, prostate disease, protocols and guidelines, urological tumours
2044-6055
Clark, Emma
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Morton, Miranda
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Sharma, Shriya
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Fisher, Holly
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Howel, Denise
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Walker, Jenn
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Wood, Ruth
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Hancock, Helen
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Maier, Rebecca
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Marshall, John
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Bahl, Amit
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Crabb, Simon
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Jain, Suneil
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Pedley, Ian
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Jones, Rob
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Staffurth, John
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Heer, Rakesh
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Clark, Emma
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Morton, Miranda
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Sharma, Shriya
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Fisher, Holly
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Howel, Denise
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Walker, Jenn
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Wood, Ruth
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Hancock, Helen
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Maier, Rebecca
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Marshall, John
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Bahl, Amit
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Crabb, Simon
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Jain, Suneil
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Pedley, Ian
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Jones, Rob
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Staffurth, John
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Heer, Rakesh
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Clark, Emma, Morton, Miranda, Sharma, Shriya, Fisher, Holly, Howel, Denise, Walker, Jenn, Wood, Ruth, Hancock, Helen, Maier, Rebecca, Marshall, John, Bahl, Amit, Crabb, Simon, Jain, Suneil, Pedley, Ian, Jones, Rob, Staffurth, John and Heer, Rakesh (2019) Prostate cancer androgen receptor splice variant 7 biomarker study - A multicentre randomised feasibility trial of biomarker-guided personalised treatment in patients with advanced prostate cancer (the VARIANT trial) study protocol. BMJ Open, 9 (12), [e034708]. (doi:10.1136/bmjopen-2019-034708).

Record type: Article

Abstract

Introduction Prostate cancer is the most common male cancer with one in four developing non-curable metastatic disease. Initial treatment responses to hormonal therapies are transient and further management options lie between (1) further hormone therapy or (2) a non-hormonal approach involving additional chemotherapy or molecular radiotherapy (radium-223). There is no clear rationale for choosing between these mechanistically different treatment approaches. The biology of hormone resistance is driven through abnormal androgen receptor activity and we can assay this through a blood test measuring androgen receptor variant 7 (AR-V7) expression in circulating tumour cells. Despite increasing evidence supporting AR-V7's role as a prognostic marker, the clinical utility of such measures remains unknown in helping personalise treatment decisions. Methods and design The VARIANT feasibility trial is a pragmatic design, to be run over 18 months with participants randomised into the intervention arm receiving biomarker (AR-V7) guided clinical treatment and participants randomised into the control arm with conventional standard management (no biomarker guidance). AR-V7 positive participants (likely to be insensitive to further hormone treatment) will receive chemotherapy or in other cases radium-223 (where routinely available). Seventy male ≥18 years old participants with metastatic castrate resistant prostate cancer clinically indicated to proceed to further hormone therapy or chemotherapy, will be recruited from three National Health Service Trusts based in England, Scotland and Wales. The feasibility primary outcome is willingness of patients to be randomised and clinicians to recruit to a biomarker-based treatment strategy, with trial data informing the basis of a definitive and appropriately powered randomised control trial. Ethics and dissemination Formal ethics review was undertaken with a favourable opinion, through Wales NRES Committee 2 18/WA/0419. Findings to be disseminated through patient and professional organisations that have expressed their support, media outlets and peer-reviewed journal publication. Trial registration number ISRCTN10246848; pre-results

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Accepted/In Press date: 22 November 2019
Published date: 18 December 2019
Keywords: adult oncology, cell biology, prostate disease, protocols and guidelines, urological tumours

Identifiers

Local EPrints ID: 437195
URI: http://eprints.soton.ac.uk/id/eprint/437195
ISSN: 2044-6055
PURE UUID: 63695c38-5648-41e2-9918-e48302a7bb57
ORCID for Simon Crabb: ORCID iD orcid.org/0000-0003-3521-9064

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Date deposited: 21 Jan 2020 17:35
Last modified: 18 Mar 2024 02:57

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Contributors

Author: Emma Clark
Author: Miranda Morton
Author: Shriya Sharma
Author: Holly Fisher
Author: Denise Howel
Author: Jenn Walker
Author: Ruth Wood
Author: Helen Hancock
Author: Rebecca Maier
Author: John Marshall
Author: Amit Bahl
Author: Simon Crabb ORCID iD
Author: Suneil Jain
Author: Ian Pedley
Author: Rob Jones
Author: John Staffurth
Author: Rakesh Heer

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