Clinical trial NCT03124433: Neoadjuvant Apalutamide (ARN509) and Radical Prostatectomy in Treatment of Intermediate to High Risk Prostate Cancer
Official title: Neoadjuvant Apalutamide (ARN509) and Radical Prostatectomy in the Treatment of Intermediate to High Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer of the Prostate
Keywords: prostate cancer
prostatectomy, retropubic
Androgen Receptor Antagonists
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
First posted: 2017-04-21
Enrollment: 30
Sex: MALE
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with pathological downstaging after neodjuvant apalutamide followed by radical prostatectomy
timeFrame: 24 weeks
measure: Proportion of patients with biochemical treatment response following neoadjuvant apalutamide and radical prostatectomy
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of patients who report significant adverse effects after 12 weeks of neoadjuvant apalutamide
timeFrame: 12 weeks
measure: The proportion of patients with peri-operative complications following neoadjuvant apalutamide and radical prostatectomy
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Department of Urology
Study officials:
affiliation: Singapore General Hospital
name: Lui Shiong Lee, MBBS,MRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yang X, Allen JC, Aslim EJ, Tay KJ, Yuen SPJ, Kanesvaran R, Chua MLK, Chong TW, Ho SSH, Lee LS. Patient-reported outcomes of a phase II neoadjuvant apalutamide (ARN-509) and radical prostatectomy in treatment of intermediate- to high-risk prostate cancer (NEAR) trial. Int J Urol. 2022 Nov;29(11):1322-1330. doi: 10.1111/iju.14994. Epub 2022 Aug 24.
citation: Lee LS, Sim AYL, Ong CW, Yang X, Ng CCY, Liu W, Rajasegaran V, Lim AMS, Aslim EJ, Ngo NT, Khor LY, Kanesvaran R, Allen JCJ, Tay KJ, Yuen JSP, Chong TW, Ho SSH, Teh BT, Chua MLK. NEAR trial: A single-arm phase II trial of neoadjuvant apalutamide monotherapy and radical prostatectomy in intermediate- and high-risk prostate cancer. Prostate Cancer Prostatic Dis. 2022 Apr;25(4):741-748. doi: 10.1038/s41391-022-00496-8. Epub 2022 Jan 28.