A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC

Study Overview
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Brief Summary
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The purpose of this study is to determine if the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.

Detailed Description
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This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multinational, multicenter study of apalutamide in participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days before randomization), Treatment Phase (28 day treatment cycles until disease progression or the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until 30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event of a positive study result and notification of unblinding at either of the interim analyses or at the final analysis, participants in the treatment Phase will have the opportunity to enroll in an Open-label Extension Phase, which will allow participants to receive active drug (apalutamide) for approximately 3 years. Participants who are receiving apalutamide in the Open-label Extension Phase may continue receiving apalutamide in the Long-term Extension (LTE) Phase if they will continue to derive benefit from treatment (based on investigator assessment). Participants' safety will be monitored throughout the study.

Official Title
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A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Subjects With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Apalutamide
* Drug: Placebo
* Drug: Androgen Deprivation Therapy (ADT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of prostate adenocarcinoma as confirmed by the investigator Metastatic disease documented by greater than or equal to (>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI) Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1 Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel <=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (<=) 6 months of ADT prior to randomization Allowed prior treatments for localized prostate cancer (all treatments must have been completed >= 1 year prior to randomization) a) <= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy,lymph node dissection, and systemic therapies Exclusion Criteria: Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate Known brain metastases Lymph nodes as only sites of metastases Visceral (ie, liver or lung) metastases as only sites of metastases Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer History of seizures or medications known to lower seizure threshold

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apalutamide plus ADT<br>Participants will receive apalutamide 240 milligram (mg) (4X 60 mg tablets) with ADT. | Drug: Apalutamide<br>* Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.<br>* Other names: ARN-509;Drug: Androgen Deprivation Therapy (ADT)<br>* All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.<br>|
| Experimental: Placebo plus ADT<br>Participants will receive matching Placebo with ADT. | Drug: Placebo<br>* Participants will receive Placebo orally once daily in each 28 day treatment cycles.<br>Drug: Androgen Deprivation Therapy (ADT)<br>* All participants will receive and remain on a stable regimen of ADT (gonadotropin releasing hormone analog [GnRHa] or surgical castration). The choice of the GnRHa (agonist or antagonist) will be at discretion of the Investigator. Dosing (dose and frequency of administration) will be consistent with the prescribing information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression-free Survival (rPFS) | rPFS as assessed by the investigator was defined as the duration from the date of randomization to the date of first documentation of radiographic progressive disease or death due to any cause, whichever occurred first. Radiographic progressive disease was defined as progression of soft tissue lesions measured by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by modified Response evaluation criteria in solid tumors (RECIST) 1.1. | Up to 35 months | 
| Overall Survival (OS) | OS was defined as the time from date of randomization to date of death from any cause. | Up to 57 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Initiation of Cytotoxic Chemotherapy | Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer. | Up to 57 months | 
| Time to Pain Progression | Time to pain progression was defined as the time from the date of randomization to the date of the first observation of pain progression. Pain progression was defined as an average increase by 2 points from baseline to greater than (>) 4 on the Brief Pain Inventory - Short Form (BPI-SF) worst pain intensity (item 3) with no decrease in opioids confirmed greater than equal to (>=) 3 weeks apart or initiation of chronic opioids, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3 (worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where 0 indicates No pain and 10 indicates Pain as bad as you can imagine. A lower score is better. | Up to 57 months | 
| Time to Chronic Opioid Use | Time to chronic opioid use was defined as the time from date of randomization to the first date of confirmed chronic opioid use. For participants entering the study without receiving opioids, chronic opioid use was defined as administration of opioid analgesics lasting for greater than or equal to (>=) 3 weeks for oral or >=7 days for non-oral formulations. For participants entering the study already receiving opioids, chronic opioid use was defined as a >=30 percent (%) increase in total daily dose of the opioid analgesics lasting for >= 3 weeks for oral or >= 7 days for non-oral formulation. | Up to 57 months | 
| Time to Skeletal-related Event (SRE) | Time to SRE was defined as the time from the date of randomization to the date of the first observation of an SRE. A SRE was defined as the occurrence of either a pathological fracture, or spinal cord compression, or radiation to bone, or surgery to bone. | Up to 57 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, JNJ-56021927, Androgen Deprivation Therapy, ARN-509, Apalutamide, TITAN, Metastatic Hormone-sensitive Prostate Cancer