Advanced metastatic prostate cancer Cancer Malignant neoplasm of prostate
Conditions
Interventions
Patients who fulfil the eligibility criteria will be randomised (using a ratio of 1:1) to:
Intervention: AR-V7 biomarker-guided personalised clinical treatment (AR-V7+ve : chemotherapy or radium-223,
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically proven diagnosis of adenocarcinoma of the prostate 2. Radiographic and/or histological and/or cytological evidence of metastatic disease 3. Castrate levels of testosterone and documented ongoing medical or surgical castration. Testosterone level =50ng/dl /1.73 nmol/L and maintaining on androgen suppression therapy. 4. Disease progression since the last change in therapy defined by one or more of the following: 4.1. PSA progression as defined by the prostate cancer working group 3 (PCWG3) criteria. This must be based on a series of at least 3 readings, each at least 7 days apart demonstrating rising PSA. The 3rd reading must be = 2ng/ml. In the event where an intermediate reading is lower than a previous reading, then the patient will still be eligible (i.e. the 3 readings do not need to be consecutive). The first of the three readings must have been obtained after commencing the previous systemic therapy, or, in the case of androgen receptor antagonists, after discontinuing 4.2. Bone disease progression as determined by the local radiology/ multidisciplinary team 4.3. Radiographic progression of nodal or visceral metastases as determined by the local radiology/ multidisciplinary team 5. Suitable for treatment with at least one novel hormonal treatment (with available treatments abiraterone acetate or enzalutamide) and one non-hormonal therapy (with available treatments docetaxel, cabazitaxel or radium-223). At least one of each type of treatment must be available to the patient 6. At least two high risk features 6.1. Age 6 months 8. Aged 18 years or over 9. Provision of written informed consent, including consent for bio-banking of blood samples at the NICR
Exclusion criteria
Exclusion criteria: 1. Histological variants of prostate cancers with small cell or neuroendocrine features 2. Prior or current malignancy (except adenocarcinoma of the prostate) with an estimated = 30% chance of relapse/progression within next 2 years 3. Previously identified brain metastases or spinal cord compression unless treated with full functional recovery 4. Administration of an investigational agent within 30 days of first dose of trial medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 propor | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
England, Scotland, United Kingdom, Wales
Contacts
Public ContactShriya Sharma
Outcome results
None listed