Have you or your loved ones been diagnosed with prostatic neoplasms?
You may be eligible to participate in a prostatic neoplasms clinical trial.
Have you or your loved ones been diagnosed with prostatic neoplasms? You may be eligible to participate in a prostatic neoplasms clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Prostatic Neoplasms Clinical Trial
Have you or your loved ones been diagnosed with prostatic neoplasms?
You may be eligible to participate in a prostatic neoplasms clinical trial.
Have you or your loved ones been diagnosed with prostatic neoplasms? You may be eligible to participate in a prostatic neoplasms clinical trial.
Recruiting
Male
18 Years +
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.
Details for the study
Brief Title
A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
Official Title
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
Brief Summary
The purpose of this study is to determine if treatment with apalutamide plus androgen <br /> deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph node <br /> dissection (pLND) in participants with high-risk localized or locally advanced prostate <br /> cancer results in an improvement in pathological complete response (pCR) rate and <br /> metastasis-free survival (MFS) 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. An open-label sub-study
comparing apalutamide plus ADT before and after RP with pLND with standard of care treatment
will be initiated at selected sites upon notification by the sponsor.
Treatments and/or Procedures
Androgen deprivation therapy ADT
Participants will receive a stable regimen of ADT - gonadotropin-releasing hormone analog (agonist or antagonist) (GnRHa). ADT is a kind of hormone therapy for prostate cancer. GnRHa will be administrated to achieve and maintain sub-castrate concentrations of testosterone (50 nanogram per deciliter [ng/dL]).
Apalutamide
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.
Placebo
Participants will receive matching placebo oral tablets daily.
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Metastasis-Free Survival (MFS)
MFS is defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Primary
Percentage of Participants with Pathologic complete response (pCR)
pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.
Secondary
Number of Participants with Treatment Compliance Rate
Number of participants who are complaint with study treatment will be assessed.
Secondary
Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability
Number of participants with physical examinations (including general appearance of the participant, height, weight, and examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities, musculoskeletal system, lymphatic system, and nervous system) abnormalities will be reported.
Secondary
Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability
Number of participants with vital signs (including body temperature, heart rate, respiratory rate, and blood pressure) abnormalities will be reported.
Secondary
Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability
Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.
Secondary
MFS Based on Conventional Imaging
MFS based on conventional imaging, defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis on CT/MRI and bone scan by radiology BICR, pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Secondary
Time to Distant Metastasis (TTDM)
TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.
Secondary
Time to Subsequent First Treatments (TTST-1)
TTST-1 is defined as the time from randomization to the date of first subsequent therapy.
Secondary
Event Free Survival (EFS)
EFS defined as time from randomization to any of the following events: biochemical failure (BCF); or local or regional recurrence by BICR or histopathological assessment; or distant metastasis by BICR or histopathological assessment; or death.
Secondary
Prostate Specific Antigen (PSA)-Free Survival
PSA-free survival with testosterone recovery defined as the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with pelvic lymph node dissection or death, whichever occurs first.
Secondary
Number of Participants with Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Study Criteria
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
investigator
- 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)
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