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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1,052
Participants will receive apalutamide 240 mg (4 x 60 mg) tablets orally once daily in each 28 day treatment cycles.
Participants will receive Placebo orally once daily in each 28 day treatment cycles.
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.
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.
Time frame: Up to 35 months
Overall Survival (OS)
OS was defined as the time from date of randomization to date of death from any cause.
Time frame: Up to 57 months
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.
Time frame: 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.
Time frame: Up to 57 months
Time to Chronic Opioid Use
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Homewood, Alabama, United States
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Tucson, Arizona, United States
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San Bernardino, California, United States
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San Diego, California, United States
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Denver, Colorado, United States
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Norwalk, Connecticut, United States
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Fort Myers, Florida, United States
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Chicago, Illinois, United States
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Fort Wayne, Indiana, United States
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Jeffersonville, Indiana, United States
...and 212 more locations
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.
Time frame: 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.
Time frame: Up to 57 months