Clinical trial NCT03365297: Therapeutics in Active Prostate Cancer Surveillance
Official title: Targeted Drug Intervention to Inhibit Cancer Progression in Men on Active Surveillance for Prostate Cancer. Therapeutics in Active Prostate Cancer Surveillance (TAPS01)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2017-12-07
Enrollment: 11
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single centre, single arm open labelled Phase II window study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Physiological Response
timeFrame: over a 90 day treatment period
Secondary outcomes:
measure: Patient Reported Outcomes
timeFrame: over 120 days
measure: Adverse Events
timeFrame: over 120 days
Other outcomes:
measure: Patient acceptability
timeFrame: over an estimated 1 year recruitment period
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust/Addenbrookes Hospital
state: Cambridgeshire
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust/University of Cambridge
name: Vincent J Gnanapragasam
role: PRINCIPAL_INVESTIGATOR
References: