Prostatic Neoplasms
Conditions
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) as compared to placebo plus ADT.
Interventions
DRUGApalutamide
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.
DRUGAndrogen 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 \[ng/dL\]).
DRUGPlacebo
Participants will receive matching placebo oral tablets daily.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Pathologic complete response (pCR) | Approximately 4 years | pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter. |
| Metastasis-Free Survival (MFS) | Up to 7 years and 5 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Specific Antigen (PSA)-Free Survival | Approximately 4 years | 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. |
| Event Free Survival (EFS) | Up to 7 years and 5 months | 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 to Subsequent First Treatments (TTST-1) | Up to 7 years and 5 months | TTST-1 is defined as the time from randomization to the date of first subsequent therapy. |
| Time to Distant Metastasis (TTDM) | Up to 7 years and 5 months | TTDM is defined as the time from the date of enrollment until the first date of distant metastasis. |
| MFS Based on Conventional Imaging | Up to 7 years and 5 months | 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. |
| Number of Participants with No Evidence of Disease (NED) at 4 Years | Up to 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). |
| Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability | Up to 30 days after last dose of study drug (Approximately 8 years) | Number of participants with vital signs (including body temperature, heart rate, respiratory rate, and blood pressure) abnormalities will be reported. |
| Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability | Up to 30 days after last dose of study drug (Approximately 8 years) | 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. |
| Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability | Up to 30 days after last dose of study drug (Approximately 8 years) | Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing. |
| Number of Participants with Treatment Compliance Rate | Up to 30 days after last dose of study drug (Approximately 8 years) | Number of participants who are complaint with study treatment will be assessed. |
Countries
Argentina, Australia, Brazil, Canada, Czechia, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Russia, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed