Neoadjuvant Apalutamide (ARN509) and Radical Prostatectomy in Treatment of Intermediate to High Risk Prostate Cancer

Study Overview
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Brief Summary
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This is an investigator-initiated phase II single arm trial, combining neoadjuvant apalutamide (ARN509) with radical prostatectomy, in the treatment of D'Amico intermediate to high risk organ-confined prostate cancer. Apalutamide has shown efficacy in castrate resistant prostate cancer in phase II studies and are now in phase III trials combined with radiation in organ confined disease. The primary study objectives include assessment of (i) oncological efficacy as determined by tumour downstaging and achievement of nadir PSA The secondary study objectives include(i) determination of adverse effects related to apalutamide and surgical complication rates (ii) human prostate tissue effect of apalutamide The study will recruit thirty eligible participants who will receive 12 weeks of oral apalutamide 240mg daily. This will be followed by standard-of-care radical prostatectomy. The total trial duration is 26 weeks.

Detailed Description
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This is a phase II single arm study looking at the efficacy of 12 weeks of neoadjuvant apalutamide (ARN 509), combined with standard-of-care radical prostatectomy, for D'Amico intermediate to high risk prostate cancer patients. The phases of the study will include: screening, treatment and follow-up phases. Safety will be monitored throughout the study.

Official Title
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Neoadjuvant Apalutamide (ARN509) and Radical Prostatectomy in the Treatment of Intermediate to High Risk Prostate Cancer

Conditions
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Cancer of the Prostate

Intervention / Treatment
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* Drug: Apalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically diagnosed primary adenocarcinoma of the prostate gland non-metastatic D'Amico intermediate to high risk patients undergoing radical prostatectomy as primary definitive therapy no known hypersensitivity to the study drug able to swallow study drug as whole tablets Exclusion Criteria: presence of small cell, neuroendocrine or ductal differentiation at needle biopsy individuals with prior pelvic irradiation therapy for any form of pelvic malignancy patients with psychiatric conditions requiring anti-psychotic therapy, or preventing the provision of informed consent renal impairment with serum creatinine more than twice the upper limit of normal Other prior malignancy less than or equal to 5 years prior to recruitment ECOG performance status 2 or poorer

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant apalutamide<br>Oral apaluatmide 240mg daily for 12 weeks followed by standard of care robotic radical prostatectomy and pelvic node dissection | Drug: Apalutamide<br>* Participants will receive oral apalutamide 240mg daily for 12 weeks<br>* Other names: ARN509;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with pathological downstaging after neodjuvant apalutamide followed by radical prostatectomy | This is described as residual cancer burden and treatment response group on histopathology after neoadjuvant apalutamide and radical prostatectomy | 24 weeks | 
| Proportion of patients with biochemical treatment response following neoadjuvant apalutamide and radical prostatectomy | Patients who attain serum PSA levels below 0.03microg/L | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who report significant adverse effects after 12 weeks of neoadjuvant apalutamide | Adverse effects as defined by CTCAE criteria grade 3 and above | 12 weeks | 
| The proportion of patients with peri-operative complications following neoadjuvant apalutamide and radical prostatectomy | The level of complications defined by Clavien-Dindo classification | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, prostatectomy, retropubic, Androgen Receptor Antagonists