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
Description
Brief Summary
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) based on conventional imaging, as compared to placebo plus
ADT.
Detailed Description
High-risk prostate cancer accounts for approximately 15 percent (%) of newly diagnosed
prostate cancers. A systemic therapy that eradicates micrometastatic disease is needed to
improve survival in high-risk participants undergoing RP with pLND. It is hypothesized that
androgen blockade prior to and after RP with pLND may improve outcomes for participants at
the highest risk for recurrence. This study is designed to evaluate if androgen blockade
administered prior to and after RP with pLND will increase the rate of pathological complete
response (pCR) and lead to better overall outcomes. ERLEADA (apalutamide, also known as
JNJ-56021927 and ARN-509) is an orally available, non-steroidal small molecule, which acts as
a potent and selective antagonist of the androgen receptor (AR), currently being developed
for the treatment of prostate cancer. The study includes screening phase (approximately up to
35 days before randomization), treatment phase (the planned Treatment Phase will include a
total of 12 treatment cycles of apalutamide or placebo; 6 cycles prior to RP with pLND (Cycle
1 through Cycle 6) and 6 cycles after RP with pLND (Cycle 7 through Cycle 12). Cycle 1 Day 1
will start within 3 days after randomization) and follow-up phase. The end of study (study
completion) is defined as last participant assessment at study site with approximate study
duration of 8 years. Participants will undergo efficacy, pharmacokinetics and biomarker
evaluations. The safety will be monitored throughout the study.
Phase
N/AInclusion and Exclusion 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 investigator
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Contraceptive use by men and female partners of men 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
- 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) signature
- 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
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.
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