The University of Southampton
University of Southampton Institutional Repository

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
524dafd7-6620-480e-a5dc-fb3a7c629e69
Morton, Miranda
3a0e2aae-f3cc-44c1-a6c3-59079dc0cdf5
Sharma, Shriya
76333a16-ffb0-457a-9eae-2457bcf4ee8b
Fisher, Holly
ae099ea0-3b83-4509-86c5-d2c5d5d27168
Howel, Denise
d5573d80-20b2-4ba5-8d23-97652ed109b5
Walker, Jenn
babdff7e-1bc4-4ab7-a3e8-334701df1295
Wood, Ruth
fb4e06da-316d-44b0-a412-dc9c5cd66f73
Hancock, Helen
1f77e861-0aa5-431b-b1cb-ad3668e6dad2
Maier, Rebecca
a632feaf-c6e4-4857-abdb-18c551399be3
Marshall, John
b89ab902-f169-4fc2-9f06-091ef8ed7926
Bahl, Amit
98bd0c14-6b4e-4d78-882e-42bfc42e7005
Crabb, Simon
bcd1b566-7677-4f81-8429-3ab0e85f8373
Jain, Suneil
4b0523b3-2bab-4ba4-9b53-3c83f845e937
Pedley, Ian
bf39aa94-1d4d-4c73-b334-e0cbafb7f6cb
Jones, Rob
cd0b6c2a-900e-40a6-8011-2cebf14d632e
Staffurth, John
51734078-ea1f-4188-8d32-75f786921586
Heer, Rakesh
c659dbeb-c1c2-48e9-b0e5-01e52dd85144
Clark, Emma
524dafd7-6620-480e-a5dc-fb3a7c629e69
Morton, Miranda
3a0e2aae-f3cc-44c1-a6c3-59079dc0cdf5
Sharma, Shriya
76333a16-ffb0-457a-9eae-2457bcf4ee8b
Fisher, Holly
ae099ea0-3b83-4509-86c5-d2c5d5d27168
Howel, Denise
d5573d80-20b2-4ba5-8d23-97652ed109b5
Walker, Jenn
babdff7e-1bc4-4ab7-a3e8-334701df1295
Wood, Ruth
fb4e06da-316d-44b0-a412-dc9c5cd66f73
Hancock, Helen
1f77e861-0aa5-431b-b1cb-ad3668e6dad2
Maier, Rebecca
a632feaf-c6e4-4857-abdb-18c551399be3
Marshall, John
b89ab902-f169-4fc2-9f06-091ef8ed7926
Bahl, Amit
98bd0c14-6b4e-4d78-882e-42bfc42e7005
Crabb, Simon
bcd1b566-7677-4f81-8429-3ab0e85f8373
Jain, Suneil
4b0523b3-2bab-4ba4-9b53-3c83f845e937
Pedley, Ian
bf39aa94-1d4d-4c73-b334-e0cbafb7f6cb
Jones, Rob
cd0b6c2a-900e-40a6-8011-2cebf14d632e
Staffurth, John
51734078-ea1f-4188-8d32-75f786921586
Heer, Rakesh
c659dbeb-c1c2-48e9-b0e5-01e52dd85144

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

Text
e034708.full - Version of Record
Available under License Creative Commons Attribution.
Download (535kB)

More information

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

Catalogue record

Date deposited: 21 Jan 2020 17:35
Last modified: 06 Jun 2024 01:41

Export record

Altmetrics

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×