Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: biomarkers; castration-resistant; feasibility studies; male; prostatic neoplasms.
In advanced prostate cancer patients are commonly treated with hormone therapy to control the cancer growth. Eventually this treatment stops working, and the next steps involve treatment with either more advanced hormone therapy (abiraterone and enzalutamide) or with chemotherapy/radiotherapy. The VARIANT trial used a blood test to check for a marker in the blood called the AR-V7 protein which may help predict which treatment option is better in these patients. By doing this trial we wanted to explore if patients and their doctors were willing to use this test to help decide the best treatment. We planned to recruit 70 men for the study. Patients who agreed to take part were put into one of two groups: (1) treatment guided by the AR-V7 test or (2) treatment as usual, decided by both doctor and patient. Blood samples were collected when the patient agreed to take part in the trial (after signing their consent), at 12 weeks and at 24 weeks after they started treatment. The blood samples were sent to the Newcastle University labs to test for AR-V7 positivity. Extra blood samples that were not used were stored in a biobank to be used in future prostate cancer research. Participants were asked to complete questionnaires throughout the trial. The trial took place across three NHS organisations across the UK, in Newcastle, Cardiff and Glasgow. The trial was planned to start recruiting participants at all three sites in October 2018. Unfortunately, due to unforeseen delays recruitment did not start until July 2019 and all three sites did not open until February 2020. A total of 12 patients were recruited. The trial showed patients were willing to be randomised to the trial to allow their treatment to be guided by a blood test. Unfortunately, due to a number of delays and difficulties with recruitment and a change in the standard treatment the study did not fully meet its outcomes.
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