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 addi...
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BMJ Publishing Group
2019-12-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/9/12/e034708.full |
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| author | John Marshall Ruth Wood Denise Howel Emma Clark Rakesh Heer John Staffurth Miranda Morton Shriya Sharma Holly Fisher Jenn Walker Helen Hancock Rebecca Maier Ian Pedley Rob Jones |
| author_facet | John Marshall Ruth Wood Denise Howel Emma Clark Rakesh Heer John Staffurth Miranda Morton Shriya Sharma Holly Fisher Jenn Walker Helen Hancock Rebecca Maier Ian Pedley Rob Jones |
| author_sort | John Marshall |
| collection | DOAJ |
| description | 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 |
| format | Article |
| id | doaj-art-956a579460664650bf760caa44e4f7d3 |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2019-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-956a579460664650bf760caa44e4f7d32025-08-20T02:51:03ZengBMJ Publishing GroupBMJ Open2044-60552019-12-0191210.1136/bmjopen-2019-034708Prostate 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 protocolJohn Marshall0Ruth Wood1Denise Howel2Emma Clark3Rakesh Heer4John Staffurth5Miranda Morton6Shriya Sharma7Holly Fisher8Jenn Walker9Helen Hancock10Rebecca Maier11Ian Pedley12Rob Jones13UK National Screening Committee, Public Health England, London, UK1Newcastle University, UKPopulation Health Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UKTranslational and Clinical Research Institute, NU Cancer, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UKImperial College London NHS Trust, London, UKResearch, Velindre Cancer Centre, Cardiff, Cardiff, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK7 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKPopulation Health Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK1 Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UKNewcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UKAcademic Cardiovascular Unit, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UKNewcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, Newcastle upon Tyne, UKUniversity of Glasgow, Glasgow, Glasgow, UKIntroduction 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-resultshttps://bmjopen.bmj.com/content/9/12/e034708.full |
| spellingShingle | John Marshall Ruth Wood Denise Howel Emma Clark Rakesh Heer John Staffurth Miranda Morton Shriya Sharma Holly Fisher Jenn Walker Helen Hancock Rebecca Maier Ian Pedley Rob Jones 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/9/12/e034708.full |
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