A Study of Apalutamide in Chinese Participants With Non Metastatic Castration Resistant Prostate Cancer (NM-CRPC)

Study Overview
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Brief Summary
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The purpose of this study is to compare the improvement in time to prostate specific antigen (PSA) progression (TTPP, as defined by Prostate Cancer Working Group 2 [PCWG2]) of apalutamide versus placebo in Chinese participants with high-risk non-metastatic castration resistant prostate cancer (NM-CRPC).

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IV Study of Apalutamide in Chinese Participants With Non-Metastatic Castration-Resistant Prostate Cancer (NM-CRPC)

Conditions
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Prostatic Neoplasms

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: Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as prostate-specific antigen doubling time (PSADT) less than or equals to (<=) 10 months. PSADT is calculated using at least 3 prostate-specific antigen (PSA) values obtained during continuous androgen deprivation therapy (ADT) Castration-resistant prostate cancer (PC) demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA greater than (>) 2 nanogram per milliliter (ng/mL) Surgically or medically castrated, with testosterone levels of less than (<) 50 nanogram per deciliter (ng/dL). If the participant is medically castrated, continuous dosing with gonadotropin releasing hormone analog (GnRHa) must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone Participants who received a first-generation anti-androgen (example: bicalutamide, flutamide, nilutamide) must have at least a 4-week washout prior to randomization and must show continuing disease progression (an increase in PSA) after washout At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization Exclusion Criteria: Presence of distant metastases, including central nervous system (CNS) and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes <2 centimeter in short axis (N1) located below the iliac bifurcation are allowed Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis, due to primary tumor (example, tumor obstruction of bladder trigone) Prior treatment with cytochrome P450 17 alpha-hydroxylase/17,20-lyase (CYP17) inhibitors (example: abiraterone acetate, orteronel, galerterone, ketoconazole, aminoglutethimide) for PC Prior chemotherapy for PC, except if administered in the adjuvant/neoadjuvant setting Prior treatment with second generation anti-androgens (example, enzalutamide) History of seizure or condition that may pre-dispose to seizure (example: prior stroke within 1 year prior to randomization, brain arteriovenous malformation, schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apalutamide 240 milligram (mg) plus ADT<br>Participants will receive apalutamide 240 mg orally daily from Day 1 of Cycle 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study along with androgen-deprivation therapy (ADT). Each treatment cycle will consist of 28 days. | Drug: Apalutamide<br>* Apalutamide 240 mg (4*60 mg tablets) will be administrated orally once daily.<br>* Other names: ARN-509;Drug: Androgen-deprivation Therapy (ADT)<br>* Participants will continue to receive ADT with gonadotrophin-releasing hormone agonists (GnRHa) who have not been surgically castrated.<br>|
| Placebo Comparator: Placebo plus ADT<br>Participants will receive matching placebo daily along with ADT from Cycle 1 Day 1 until disease progression, unacceptable toxicity, withdrawal of consent, death or termination of the study. Participants who do not have distant metastasis will switch to treatment with apalutamide after completion of 5 cycles of placebo treatment. Participants who have prostate-specific antigen (PSA) progression prior to completion of 5 cycles of study treatment, will cross over to apalutamide at the time of PSA progression. Each treatment cycle will consist of 28 days. | Drug: Placebo<br>* Matching placebo will be administered orally.<br>Drug: Androgen-deprivation Therapy (ADT)<br>* Participants will continue to receive ADT with gonadotrophin-releasing hormone agonists (GnRHa) who have not been surgically castrated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Prostate Specific Antigen (PSA) Progression (TTPP) | TTPP is defined as the time from randomization to the first date of documented PSA progression based on Prostate Cancer Working Group 2 (PCWG2) criteria. | Up to 4.9 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Event (AEs) as a Measure of Safety and Tolerability | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 6.6 years | 
| Number of Participants with Clinical Laboratory Abnormalities | Number of participants with clinical laboratory abnormalities will be reported. | Up to 6.6 years | 
| Prostate Specific Antigen (PSA) Response Rate | PSA response rate is defined as the percentage of participants who achieved at least a 50 percent (%) decline in PSA value from baseline assessed by a central laboratory according to PCWG2 criteria. | Up to 6.6 years | 
| Plasma Concentrations of Apalutamide and its Metabolite (N-desmethyl apalutamide) | Plasma concentrations of apalutamide and its metabolite (N-desmethyl apalutamide) will be assessed after single dose and at steady-state. | Presdose (Day 1 of Cycles 1, 2, 3, 6); 2 hours postdose (Day 1 of Cycles 1 and 3) (each cycle is of 28 days) |