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.

introductionProstate 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

designThe 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.