A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Apalutamide in Subjects with High-risk, Localized or Locally Advanced Prostate Cancer Who are Candidates for Radical Prostatectomy

Protocol # :
Prostatic Neoplasms
Disease Sites
Principal Investigator
Taplin, Mary-Ellen
Site Investigator
Bubley, Glenn
Site Research Nurses
Aspinwall, Sheridan
Aspinwall, Sheridan
Bretta, Katherine, v.
Carey, Margaret, M.
Creaton, Eileen
Gundy, Kathryn, E.
Kabarame, Liliane
Kelleher, Kaitlin
Lagerstedt, Elizabeth
Leisner, Claire
Mingrino, Sage
Morse, Linda, K.
Pace, Amanda
Polinski, Karen
Porter, Kathryn
Prisby, Judith
Theodore, Catherine
Walsh, Meghara

Trial Description

The purpose of this study is to determine if treatment with apalutamide plus androgen
deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph
node dissection (pLND) in participants with high-risk localized or locally advanced
prostate cancer results in an improvement in pathological complete response (pCR) rate
and metastasis-free survival (MFS) as compared to placebo plus ADT.

Eligibility Requirements

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- High-risk disease defined by a total Gleason Sum Score greater than equal to (>=)
4+3 (=Grade Groups [GG] 3 5) and >=1 of the following 4 criteria: a) Any combination
of Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in >= 6 systematic cores
(with >=1 core Gleason Score 8 [4+4 or 5+3] included); b) Any combination of Gleason
Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in >=3 systematic cores and
Prostate-specific antigen (PSA) >=20 ng/mL (with >= 1 core Gleason Score 8 [4+4 or
5+3] included); c) Gleason Score >=9 (=GG 5) in at least 1 systematic or targeted
core; d) At least 2 systematic or targeted cores with continuous Gleason Score >=8
(=GG 4), each with > 80 percent (%) involvement

- Candidate for radical prostatectomy with pelvic lymph node dissection as per the

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

- Contraceptive use by male participants (and female partners of male participants
enrolled in the study who are of childbearing potential or are pregnant) should be
consistent with local regulations regarding the use of contraceptive methods for
participants participating in clinical studies

- Able to receive androgen deprivation therapy (ADT) for at least 13 months

Exclusion Criteria:

- Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease
below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of
distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal
disease (clinical N stage; N1 versus N0) will be assessed by central radiological
review. Participants are considered eligible only if the central radiological review
confirms clinical stage M0

- (a) Prior treatment with androgen receptor antagonists; (b) Treatment with
gonadotropin-releasing hormone analog (GnRHa) prior to informed consent form (ICF)

- History of prior systemic or local therapy for prostate cancer, including pelvic
radiation for prostate cancer

- Use of any investigational agent less than or equals to (<=)4 weeks prior to
randomization or any therapeutic procedure for prostate cancer at any time

- Major surgery <=4 weeks prior to randomization

- Any of the following within 12 months prior to first dose of study drug: severe or
unstable angina, myocardial infarction, symptomatic congestive heart failure,
arterial or venous thromboembolic events (example, pulmonary embolism,
cerebrovascular accident including transient ischemic attacks), or clinically
significant ventricular arrhythmias or New York Heart Association Class II to IV
heart disease; uncomplicated deep vein thrombosis is not considered exclusionary