Therapeutics in Active Prostate Cancer Surveillance

Study Overview
=================
Brief Summary
-----------------
Testing if short-term use of apalutamide can reduce image defined tumour volumes in men with detectable lesion on multi-parametric Magnetic Resonance Imaging (mpMRI) and being managed by Active Surveillance. The trial will also evaluate the tolerability and side effect profile of men on AS using short term apalutamide and patient acceptability as a therapeutic strategy, as well as determining feasibility of a larger prospective randomised trial of apalutamide.

Detailed Description
-----------------
The numbers of men diagnosed with prostate cancer in the United Kingdom (UK) and worldwide is increasing. In the UK 46,690 men were diagnosed in 2014 alone and it is estimated this figure will be closer to 70,000 by 2030. A significant proportion of these men will present with organ confined and low or intermediate risk disease. There is increasing recognition that many men with low and intermediate risk prostate cancer do not need immediate radical therapy. There is sufficient evidence that pharmacological intervention used as short-term therapy in men with low to intermediate-risk disease can inhibit the growth of prostate tumours and delay or remove the need for radical therapy in men managed by active surveillance. Given the irrefutable role of the androgen receptor in prostate cancer pathogenesis it is logical to target this pathway as a method of inhibiting or delaying disease progression. This window study will be built on the known anti-androgen effects of apalutamide and investigate the efficacy of using it as a short intervention strategy to cause a physiological change in the tumour by reducing its volume. Tumour volume can be measured using the well-established place of mpMRI defined tumour volumes as a surrogate of disease presence and change. The rationale for a short duration treatment is that it will not have the long term debilitating effects of androgen deprivation on general health and prevent the onset of androgen resistance. It is anticipated that if successful, this approach could be a new therapeutic strategy for these men who otherwise are living and waiting for their disease to progress or not.

Official Title
-----------------
Targeted Drug Intervention to Inhibit Cancer Progression in Men on Active Surveillance for Prostate Cancer. Therapeutics in Active Prostate Cancer Surveillance (TAPS01)

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Apalutamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Given Informed Consent (IC) to participate Age 18 or over Eastern Cooperative Oncology Group (ECOG) status 0-2 Diagnosed with prostate cancer Patient selection of active surveillance as a management option mpMRI detectable lesion Prostate cancer on biopsy from a mpMRI defined lesion No contraindications to apalutamide Normal full blood count and normal renal and liver function tests At least 6 months since initiation of active surveillance and/or last rebiopsy date. Low or intermediate risk prostate cancer according to National Institute for Health and Care Excellence (NICE) classification M score of ≥ 3 using Prostate Imaging Reporting and Data System (PIRADS) version 2 reporting criteria Exclusion Criteria: Contraindications to apalutamide or its excipients Concurrent medication that can lower seizure threshold Prior localised therapy for prostate cancer Any prior use of androgen deprivation therapy or androgen receptor targeting agents Any prior systemic therapy for prostate cancer Patient unable to have prostate 3T mpMRI scan Presence of any pelvic or hip metalwork

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single centre, single arm open labelled Phase II window study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>apalutamide, 240mg (4x60mg tablets) orally, daily for a max. duration of 90 continuous days. | Drug: Apalutamide<br>* 240mg (4x60mg) oral tablets daily over a max. of 90 days<br>* Other names: JNJ-56021927;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physiological Response | Tumour volume downsizing/absence of lesion, as determined by mpMRI | over a 90 day treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Outcomes | Function and wellbeing using established standardised EQ-5D-5L and EORTC-QLQ30+PR25 module questionnaires | over 120 days | 
| Adverse Events | tolerability and side effect profile | over 120 days |