VARIANT: A multicentre randomised feasibility trial of implementing a biomarker-guided personalised treatment in patients with advanced prostate cancer

Current primary outcome measures as of 14/11/2019:
Primary outcome measures are related to feasibility (recruitment, retention and adherence) and will report the following;
1. The proportion of prostate cancer patients identified through clinics who meet the eligibility criteria
2. The number of patients accrued per site per month over the course of the trial
3. Baseline prevalence of AR-V7 expression in the participant cohort (this will be presented as a crude percentage of AR-V7 positivity of total participants, and in each arm)
4. The willingness of patients to be randomised (defined as the proportion of patients consenting to be randomised from all eligible patients approached about the study)
5. Compliance rate (this will be defined as the number of patients who start randomised treatment as a proportion of the number randomised)
6. The proportion of patients who: start AR-V7 recommended treatment; start treatment other than the recommended treatment; change treatment before disease progression; or withdraw. (This measure will capture information regarding patients who choose not to take recommended treatment because of strong preferences and patients who progress rapidly while waiting for treatment with a change in eligibility for treatment options).
7. The proportion of trial participants with assessable blood samples for biomarker status (which would affect treatment targeting)
8. The median time from the blood sample being drawn to:
8.1. AR-V7 result being sent back to the site
8.2. patient starting treatment (and compared with standard of care treatment)
9. The proportion of randomised patients for whom data is collected on each clinical and health economic outcome at baseline, 12 and 24 weeks.

Previous primary outcome measures:
Feasibility outcome measures:
1. The number of patients recruited per site per month over the course of the trial
2. The proportion of patients with prostate cancer identified who meet the eligibility criteria
3. The proportion of those meeting the eligibility criteria who agree to be randomised in the study
4. Baseline prevalence of AR-V7 expression in trial participants
5. The proportion of patients who: start AR-V7 recommended treatment; start treatment other than the recommended treatment; change treatment before disease progression; or withdraw. This measure will capture information regarding patients who choose not to take recommended treatment because of strong preferences and patients who progress rapidly while waiting for treatment with a change in eligibility for treatment options.
6. The proportion of trial participants with assessable blood samples for biomarker status (which would affect treatment targeting)
7. The proportion of randomised patients for whom data is collected on each clinical and health economic outcome at baseline, 12 and 24 weeks
8. The median time from drawing the blood sample for biomarker assessment to
8.1. AR-V7 result being sent back to site
8.2. Time taken to start treatment in both control and intervention arms

Current secondary outcome measures as of 14/11/2019:
Standardised clinical assessment tools used in monitoring castration-resistant prostate cancer (CRPC) disease and progression on treatment will be reported and measured as secondary outcomes.
1. Time to PSA progression: Confirmed rising PSA more than 12 weeks after randomisation. (Where there has been a decline in PSA from baseline, progression will be a 25% or greater increase, and an absolute increase of at least 2 ng/ml, from the nadir, which is confirmed by a second value obtained three or more weeks later. Where no decline from baseline is documented, progression must be a 25% or greater increase from the baseline value along with an increase in absolute value of 2 ng/ml or more. In all cases, the initial rise in PSA must occur after a minimum of 12 weeks from randomisation).
2. Clinical progression and survival within 6 months:
2.1. Number of patients who have progressed clinically at 6 months (includes change of systemic anti-cancer therapy and death from prostate cancer)
2.2. Cancer specific survival at 6 months
2.3. Overall survival at 6 months
3. Quality of life for patients with cancer assessed using EORTC QLQ-C30
4. Additional quality of life items patients with prostate cancer assessed using EORTC QLQ-PR25
5. Participant costs questionnaire measured with Health Services Questionnaire

Previous secondary outcome measures:
Clinical outcome measures:
1. Time to PSA progression: Confirmed rising PSA more than 12 weeks after randomisation. Where there has been a decline in PSA from baseline, progression will be a 25% or greater increase, and an absolute increase of at least 2ng/mL, from the nadir, which is confirmed by a second value obtained 3 or more weeks later. Where no decline from baseline is documented, progression must be a 25% or greater increase from the baseline value along with an increase in absolute value of 2 ng/mL or more. In all cases, the initial rise in PSA must occur after a minimum of 12 weeks from randomisation.
2. Clinical progression and survival within 6 months:
2.1. Number of patients who have progressed clinically at 6 months (includes change of systemic anti-cancer therapy and death from PC)
2.2. Cancer-specific survival at 6 months
2.3. Overall survival at 6 months
3. Quality of life for patients with cancer, measured using EORTC QLQ-C30 at baseline and 24 weeks after the first treatment
4. Additional quality of life items for patients with prostate cancer, measured using EORTC QLQ-PR25 at baseline and 24 weeks after the first treatment
5. Participant costs measured using Use of Health Services Questionnaire at 24 weeks after the first treatment