Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS). Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein.
We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated.
Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target.
Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials.
NIHR open research. 2023 Jan 10 [Epub]
Paul Gravestock, Emma Clark, Miranda Morton, Shirya Sharma, Holly Fisher, Jenn Walker, Ruth Wood, Helen Hancock, Nichola Waugh, Aislinn Cooper, Rebecca Maier, John Marshall, Robert Chandler, Amit Bahl, Simon Crabb, Suneil Jain, Ian Pedley, Rob Jones, John Staffurth, Rakesh Heer
Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, Tyne and Wear, NE3 3HD, UK., Translational and Clinical Research Institute, NU Cancer, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK., Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE2 4AE, UK., Population Health Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK., Velindre University NHS Trust, Cardiff, CF15 7QZ, UK., Trial Management Group, VARIANT Trial, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK., University Hospitals Bristol NHS Foundation Trust, Bristol, BS1 3NU, UK., University of Southampton, Southampton, Hampshire, SO17 1BJ, UK., Queens University Belfast, Belfast, BT7 1NN, UK., Institute of Cancer Services, University of Glasgow, Glasgow, G12 0YN, UK.