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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
2,517
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.
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 \[ng/dL\]).
Participants will receive matching placebo oral tablets daily.
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.
Time frame: Approximately 4 years
Metastasis-Free Survival (MFS)
MFS is defined as the time from randomization to the date of the occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.
Time frame: Up to 7 years and 5 months
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.
Time frame: Approximately 4 years
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.
Time frame: Up to 7 years and 5 months
Time to Subsequent First Treatments (TTST-1)
TTST-1 is defined as the time from randomization to the date of first subsequent therapy.
Time frame: Up to 7 years and 5 months
Time to Distant Metastasis (TTDM)
TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.
Time frame: Up to 7 years and 5 months
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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.
Time frame: Up to 7 years and 5 months
Number of Participants with No Evidence of Disease (NED) at 4 Years
Number of participants with NED at 4 years will be reported. NED at 4 years is defined as: (a) alive, (b) Undetectable prostate-specific antigen (PSA), (c) No distant metastasis, (d) No local or regional recurrence, (e) No subsequent therapy for prostate cancer, (f) Testosterone recovery to physiological testosterone levels, defined as 200 nanograms per deciliter (ng/dL).
Time frame: Up to 4 years
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.
Time frame: Up to 30 days after last dose of study drug (Approximately 8 years)
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.
Time frame: Up to 30 days after last dose of study drug (Approximately 8 years)
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.
Time frame: Up to 30 days after last dose of study drug (Approximately 8 years)
Number of Participants with Treatment Compliance Rate
Number of participants who are complaint with study treatment will be assessed.
Time frame: Up to 30 days after last dose of study drug (Approximately 8 years)