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

Phase 4
Active, not recruiting
Conditions
Prostatic Neoplasms
Interventions
Drug: Placebo
Drug: Androgen-deprivation Therapy (ADT)
Registration Number
NCT04108208
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
75
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Apalutamide 240 milligram (mg) plus ADTAndrogen-deprivation Therapy (ADT)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.
Placebo plus ADTPlaceboParticipants 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.
Placebo plus ADTAndrogen-deprivation Therapy (ADT)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.
Apalutamide 240 milligram (mg) plus ADTApalutamideParticipants 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.
Primary Outcome Measures
NameTimeMethod
Time to Prostate Specific Antigen (PSA) Progression (TTPP) Based on Prostate Cancer Working Group 2 (PCWG2) CriteriaFrom randomization until first documented PSA progression (up to 3 years 3 months)

Time to prostate specific antigen progression (TTPP) was defined as the time from randomization to the first date of documented PSA progression based on PCWG2 criteria. PCWG2 was defined as the PSA progression as 1) the date that a 25 percent (%) or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) or more from the Nadir was documented, which was confirmed by a second value obtained 3 or more weeks later. 2) Where no decline from baseline was documented as a 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 week of treatment. Kaplan-Meier method was used for the analysis.

Secondary Outcome Measures
NameTimeMethod
Plasma Concentration of Apalutamide and Its Metabolite (N-desmethyl Apalutamide)Presdose: Day 1 of Cycles 1, 2, 3, and 6; 2 hours postdose: Day 1 of Cycles 1 and 3
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)Up to 6 years 4 months
Number of Participants With Grade 3 or Higher Abnormalities in Laboratory ValuesUp to 6 years 4 months
Percentage of Participants Who Achieved Prostate Specific Antigen (PSA) Response (>=50% PSA Reduction)Up to 6 years 4 months

Trial Locations

Locations (27)

Hunan Cancer hospital

🇨🇳

Changsha, China

Fujian Medical University Union Hospital

🇨🇳

Fuzhou, China

Zhejiang Cancer Hospital

🇨🇳

Hang Zhou, China

The First Affiliated Hospital Zhejiang University College of Medicine

🇨🇳

Hangzhou, China

Huashan Hospital Fudan University

🇨🇳

Shanghai, China

Peking University First Hospital

🇨🇳

Beijing, China

Beijing Friendship Hospital

🇨🇳

Beijing, China

Sichuan Provincial Peoples Hospital

🇨🇳

Chengdu, China

Shanghai Zhongshan Hospital

🇨🇳

ShangHai, China

First Affiliated Hospital SooChow University

🇨🇳

Suzhou, China

TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology

🇨🇳

Wuhan, China

The First Affiliated Hospital of Xian Jiaotong University

🇨🇳

Xian, China

Beijing Hospital

🇨🇳

Beijing, China

Renji Hospital, Shanghai Jiaotong University School of Medicine

🇨🇳

Shanghai, China

Huadong Hospital Affiliated to Fudan University

🇨🇳

Shanghai, China

Sun Yat-Sen Memorial Hospital Sun Yat-sen University

🇨🇳

Guangzhou, China

Zhejiang Provincial People's Hospital

🇨🇳

Hangzhou, China

Cancer Hospital, FuDan University

🇨🇳

Shanghai, China

The Fifth People's Hospital of Shanghai, Fudan University

🇨🇳

Shanghai, China

Cancer Hospital Chinese Academy of Medical Sciences

🇨🇳

Beijing, China

Chongqing University Cancer Hospital

🇨🇳

Chongqing, China

Peking University People s Hospital

🇨🇳

Beijing, China

Peking University Third Hospital

🇨🇳

Beijing, China

The First Affiliated Hospital of Ningbo University

🇨🇳

Ningbo, China

Wuxi People s Hospital

🇨🇳

Wuxi, China

Guangzhou First Municipal People's Hospital

🇨🇳

Guangzhou, China

Nanjing Drum Tower Hospital

🇨🇳

Nanjing, China

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