A Study of Apalutamide (Adjuvant Treatment) and Androgen Deprivation Therapy (ADT) in Participants Who Have Undergone Radical Prostatectomy (RP) for Non-metastatic Prostate Cancer and Who Are at High Risk for Metastases

Study Overview
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Brief Summary
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Main Study: The purpose of main study is to assess if the combination of apalutamide and androgen deprivation therapy (ADT) in participants with high-risk localized prostate cancer improves the biochemical recurrence (BCR) free rate. Sub-study: The purpose of the sub-study is to assess if the co administration of apalutamide and relugolix is able to maintain castrate levels of testosterone.

Official Title
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A Multi-center, Open-label, Single-arm Phase 2 Study of the Adjuvant Treatment of Apalutamide and Androgen Deprivation Therapy (ADT) in Treatment-naïve Participants Who Have Undergone Radical Prostatectomy (RP) for Non-metastatic Prostate Cancer and Who Are at High Risk for Metastases

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Apalutamide
* Drug: ADT
* Drug: Relugolix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A candidate for radical prostatectomy (RP) or status post RP. Eligible to receive study intervention between Day 29 and Day 90 post-RP. Post RP prostate-specific antigen (PSA) of <= 0.2 nanograms per milliliter (ng/mL). Has not received other treatment for prostate cancer Have recovered from RP procedure and have had no worsening in cardiac risk in the peri-operative period per the clinical judgement of the investigator Adequate organ function (hepatic, renal, hematologic and cerebral) determined at the discretion of the treating physician Eastern Cooperative oncology Group (ECOG) Performance Status Score of 0 or 1 Histologically confirmed adenocarcinoma of the prostate and categorized as high risk for recurrent prostate cancer. High risk can be defined based on PSA alone or biopsy or RP specimen as follows: PSA greater than or equal to (>=) 20 ng/ml or; Gleason Score >= 9 in any core on biopsy or; Gleason Score >= 8 (4+4 or 5+3) in greater than (>) 80 percentage (%) of 2 cores on biopsy or; Gleason Score = 8 (4+4 or 5+3) in 1 core as long 5 or more other cores with minimum Gleason Score of 4+3 on biopsy. The determination of high risk may be based on pathology report of biopsy or equivalent criteria from radical prostatectomy Exclusion Criteria: History or presence of soft tissue/bone metastasis or metastasis in distant lymph nodes (pelvic lymph nodes below the iliac bifurcation that are less than (<) 2 centimeter (cm) in diameter [short axis] either radiographically or pathologically are allowed.) History of bilateral orchiectomy Received an investigational intervention <= 4 weeks before the planned first dose of study intervention History of seizure or any condition that in the opinion of the investigator may predispose to seizure or treatment with drugs known to lower the seizure threshold within 4 weeks prior to starting treatment with apalutamide Allergy or hypersensitivity to apalutamide, or excipients, unable or unwilling to take androgen deprivation therapy (ADT)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apalutamide + Androgen Deprivation Therapy (ADT)<br>In the main study, participants will receive apalutamide 240 milligram (mg) once daily orally along with ADT for 12 cycles (Each cycle is of 28 days). Participants who enrolled in the sub-study will receive apalutamide 240 mg once daily along with relugolix (a type of ADT) 120 mg once daily following a loading dose of 360 mg relugolix orally. Sub-study participants will be receiving relugolix up to Day 28 after which they will be transitioned into the main study from Cycle 2 Day 1 and will continue to receive conventional or oral ADT. | Drug: Apalutamide<br>* Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) oral tablets during the main study and sub-study.<br>* Other names: JNJ-56021927;Drug: ADT<br>* Participants will receive ADT intramuscular or subcutaneously during the main study.<br>Drug: Relugolix<br>* Participants will receive 120 mg of relugolix following a loading dose of 360 mg of (3 tablets of 120 mg each) relugolix during the sub-study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Study: Time to Biochemical Recurrence (BCR) | BCR is defined as a confirmed prostate specific antigen (PSA) greater than (>) 0.2 nanogram per milliliter (ng/ml) and time to BCR will be analyzed using Kaplan-Meier method. | Month 24 | 
| Sub-study: Percentage of Participants Maintaining Testosterone Level Less Than (<) 50 Nanograms per Deciliter (ng/dL) Through Day 28 | Percentage of participants maintaining testosterone level <50 ng/dL through Day 28 will be reported. | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Study: Time to BCR | BCR is defined as a confirmed PSA > 0.2 ng/ml and time to BCR will be analyzed using Kaplan-Meier method. | Month 12 | 
| Main Study: Time to Serum Testosterone Recovery | The testosterone recovery, defined as a serum testosterone greater than or equal to (>=)150 nanograms per deciliter (ng/dL) which will be analyzed using Kaplan-Meier method. | Months 18 and 24 | 
| Sub-study: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to Day 28 |