A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Metastatic Hormone Sensitive Prostate Cancer Clinical Trial

— ARCHES  

Official title:

A Multinational, Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02677896
• Other study ID #: 9785-CL-0335
• Secondary ID: 2015-003869-28
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 9, 2016
• Est. completion date: July 31, 2024

Study information

• Verified date: June 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to evaluate the efficacy of enzalutamide plus androgen deprivation therapy (ADT) as measured by radiographic progression-free survival (rPFS) based on central review. The study also evaluated the safety of enzalutamide plus ADT in mHSPC.

Description:

Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over placebo when added to ADT as assessed by the primary endpoint of rPFS, subjects were eligible to transition to an open-label portion of the study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1150
• Est. completion date: July 31, 2024
• Est. primary completion date: October 14, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject is considered an adult according to local regulation at the time of signing informed consent.

• Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.

• Subject has metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan (for soft tissue). Subjects whose disease spread is limited to regional pelvic lymph nodes are not eligible.

• Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).

• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Inclusion Criteria for Open-Label Extension:

• Subject received randomized double-blind treatment in ARCHES

• Subject has not met any of the discontinuation criteria in the main ARCHES protocol

• Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a bilateral orchiectomy.

• Subject is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study

• Subject and subject's female partner agree to follow contraception and sperm donation requirements in main protocol

Exclusion Criteria:

• Subject has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer (the following exceptions are permitted):

• Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;

• Subject may have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to day 1;

• Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of day 1 and no evidence of disease progression during or after the completion of docetaxel therapy;

• Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;

• Prior ADT given for < 39 months in duration and > 9 months before randomization as neoadjuvant/adjuvant therapy.

• Subject had a major surgery within 4 weeks prior to day 1.

• Subject received treatment with 5-a reductase inhibitors (finasteride, dutasteride) within 4 weeks prior to day 1.

• Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks prior to day 1.

• Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to day 1, intended for the treatment of prostate cancer.

• Subject received treatment with herbal medications that have known hormonal antiprostate cancer activity and/or are known to decrease PSA levels within 4 weeks prior to day 1.

• Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for the treatment of prostate cancer or participation in a clinical study of an investigational agent that inhibits the AR or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).

• Subject has known or suspected brain metastasis or active leptomeningeal disease.

• Subject has absolute neutrophil count < 1500/µL, platelet count < 100000/µL or hemoglobin < 10 g/dL (6.2 mmol/L).

• Subject has total bilirubin (TBL) = 1.5 x the upper limit of normal (ULN) (except subjects with documented Gilbert's disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 x the ULN .

• Subject has creatinine > 2 mg/dL (177 µmol/L).

• Subject has albumin < 3.0 g/dL (30 g/L).

• Subject has a history of seizure or any condition that may predispose to seizure.

• Subject has history of loss of consciousness or transient ischemic attack within 12 months prior to day 1.

• Subject has clinically significant cardiovascular disease.

• Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless administered at stable dose or to treat diagnosed osteoporosis

Exclusion Criteria for Open-Label Extension:

• Subject has taken commercially available enzalutamide (Xtandi).

• Subject's disease has progressed radiographically during the double-blind period of the study and treatment with study drug was stopped prior to study-wide unblinding. (Note: Subjects who progressed radiographically while in the double-blind portion of the study and continued treatment per protocol are allowed to participate in the open label extension.)

• After study-wide unblinding, subject has started any new investigational agent or anti-neoplastic therapy intended to treat prostate cancer

• Subject has any clinically significant disorder or condition including excessive alcohol or drug abuse, or secondary malignancy, which may interfere with study participation

• Subject has current or previously treated brain metastasis or active leptomeningeal disease

• Subject has a history of seizure or any condition that may increase the risk of seizure

Related Conditions & MeSH terms

• Hypersensitivity
• Metastatic Hormone Sensitive Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
Oral
• Placebo
Oral

Locations

Country	Name	City	State
Argentina	Site AR54010	Buenos Aires
Argentina	Site AR54002	Rosario	Santa Fe
Argentina	Site AR54007	San Miguel de Tucuman	Tucuman
Australia	Site AU61004	Ballarat	Victoria
Australia	Site AU61016	Camperdown	New South Wales
Australia	Site AU61015	Clayton	Victoria
Australia	Site AU61017	Parkville	Victoria
Australia	Site AU61007	St Leonards	New South Wales
Australia	Site AU61008	St. Albans	Victoria
Australia	Site AU61006	Sydney	New South Wales
Australia	Site AU61009	Tweed Heads	New South Wales
Australia	Site AU61013	Waratah	New South Wales
Australia	Site AU61001	Woodville South	South Australia
Belgium	Site BE32012	Gent	Oost-Vlaanderen
Belgium	Site BE32005	Kortrijk	West-Vlaanderen
Belgium	Site BE32008	Liege
Belgium	Site BE32001	Mons	Hainaut
Belgium	Site BE32007	Yvoir
Canada	Site CA15024	Abbotsford	British Columbia
Canada	Site CA15010	Brampton	Ontario
Canada	Site CA15016	Edmonton	Alberta
Canada	Site CA15023	Granby	Quebec
Canada	Site CA15003	Kelowna	British Columbia
Canada	Site CA15022	Kelowna	British Columbia
Canada	Site CA15021	Kingston	Ontario
Canada	Site CA15004	Montreal	Quebec
Canada	Site CA15013	Oakville	Ontario
Canada	Site CA15020	Toronto	Ontario
Chile	Site CL56007	Providencia	Santiago
Chile	Site CL56004	Reñaca	Viña Del Mar
Chile	Site CL56001	Santiago	RM
Chile	Site CL56003	Santiago
Chile	Site CL56002	Temuco	IX Region
Chile	Site CL56005	Viña Del Mar	Valparaiso
Denmark	Site DK45004	Aalborg	Nordjylland
Denmark	Site DK45005	Aarhus	Midtjylland
Denmark	Site DK45002	Copenhagen	Hovestaden
Denmark	Site DK45003	Herlev
Denmark	Site DK45008	Holstebro	Midtjylland
Denmark	Site DK45001	Odense C
Finland	Site FI35802	Helsinki	Etelä-Suomen Lääni
Finland	Site FI35805	Oulu
Finland	Site FI35806	Pietarsaari
Finland	Site FI35804	Pori	Länsi-Suomen Lääni
Finland	Site FI35803	Seinäjoki	Länsi-Suomen Lääni
Finland	Site FI35801	Tampere	Oulun Laani
Finland	Site FI35807	Turku
France	Site FR33010	Angers	Maine-et-Loire
France	Site FR33006	Bordeaux
France	Site FR33014	Caen Cedex 05
France	Site FR33003	Creteil	Val-de-Marne
France	Site FR33005	La Roche sur Yon
France	Site FR33015	Le Mans Cedex 2
France	Site FR33012	Lille Cedex
France	Site FR33007	Lyon Cedex 3
France	Site FR33011	Nimes
France	Site FR33001	Pierre Benite
France	Site FR33009	Quimper
France	Site FR33013	Saint Mande
Germany	Site DE49005	Bonn
Germany	Site DE49002	Freiburg	Baden-Württemberg
Germany	Site DE49014	Hamburg
Germany	Site DE49013	Heidelberg
Germany	Site DE49004	Nürtingen	Baden-Württemberg
Israel	Site IL97210	Beer-Sheva
Israel	Site IL97202	Haifa
Israel	Site IL97205	Haifa
Israel	Site IL97206	Jerusalem
Israel	Site IL97201	Kfar-Saba	HaMerkaz
Israel	Site IL97211	Zerifin	HaMerkaz
Italy	Site IT39009	Candiolo
Italy	Site IT39004	Cremona	Lombardia
Italy	Site IT39005	Meldola	Emilia-Romagna
Italy	Site IT39003	Milano	Lombardia
Italy	Site IT39012	Milano	Lombardia
Italy	Site IT39007	Novara	Piemonte
Italy	Site IT39006	Padova	Veneto
Italy	Site IT39008	Pisa	Toscana
Italy	Site IT39011	Trento	Trentino-Alto Adige
Japan	Site JP81010	Abeno-ku	Osaka
Japan	Site JP81006	Bunkyo-ku	Tokyo
Japan	Site JP81002	Chiba
Japan	Site JP81011	Chuo-ku	Osaka
Japan	Site JP81014	Fukuoka
Japan	Site JP81015	Fukuoka
Japan	Site JP81013	Kita-gun	Kagawa
Japan	Site JP81004	Koto-ku	Tokyo
Japan	Site JP81008	Kyoto
Japan	Site JP81001	Maebashi	Gunma
Japan	Site JP81018	Nagasaki
Japan	Site JP81020	Niigata
Japan	Site JP81012	Osakasayama	Osaka
Japan	Site JP81003	Sakura	Chiba
Japan	Site JP81016	Sendai	Miyagi
Japan	Site JP81005	Shinjuku-ku	Tokyo
Japan	Site JP81017	Ube	Yamaguchi
Japan	Site JP81019	Yamagata
Japan	Site JP81007	Yokohama	Kanagawa
Korea, Republic of	Site KR82007	Busan
Korea, Republic of	Site KR82004	Incheon
Korea, Republic of	Site KR82008	Seongnam-si	Gyeonggi-do
Korea, Republic of	Site KR82001	Seoul
Korea, Republic of	Site KR82002	Seoul
Korea, Republic of	Site KR82003	Seoul
Netherlands	Site NL31010	Alkmaar	Noord-Holland
Netherlands	Site NL31008	Amsterdam	Noord-Holland
Netherlands	Site NL31005	Eindhoven	Noord-Brabant
Netherlands	Site NL31003	Nijmegen	Gelderland
Netherlands	Site NL31007	Nijmegen	Gelderland
Netherlands	Site NL31006	Rotterdam	Zuid-Holland
Netherlands	Site NL31002	Sneek	Friesland
Netherlands	Site NL31009	Zwolle	Overijssel
New Zealand	Site NZ64002	Dunedin	South Island
New Zealand	Site NZ64004	Hamilton
New Zealand	Site NZ64008	Kensington	Northland
New Zealand	Site NZ64005	Nelson	Tasman District
New Zealand	Site NZ64003	Tauranga	Bay Of Plenty
Poland	Site PL48005	Gdansk	Pomerania
Poland	Site PL48007	Krakow	Malopolskie
Poland	Site PL48001	Myslowice
Poland	Site PL48010	Slupsk	Pomorskie
Poland	Site PL48011	Warszawa	Mazowieckie
Poland	Site PL48003	Wroclaw	Dolnoslaskie
Romania	Site RO40007	Brasov
Romania	Site RO40003	Bucharest
Romania	Site RO40006	Bucharest
Romania	Site RO40008	Cluj-Napoca	Cluj
Romania	Site RO40009	Cluj-Napoca	Cluj
Romania	Site RO40002	Floresti	Cluj
Romania	Site RO40011	Timisoara	Timis
Russian Federation	Site RU70013	Ivanovo
Russian Federation	Site RU70001	Moscow
Russian Federation	Site RU70003	Moscow
Russian Federation	Site RU70014	Moscow
Russian Federation	Site RU70006	Omsk
Russian Federation	Site RU70005	Penza
Russian Federation	Site RU70007	St. Petersburg
Russian Federation	Site RU70008	St. Petersburg
Russian Federation	Site RU70009	St. Petersburg
Russian Federation	Site RU70012	St. Petersburg
Russian Federation	Site RU70016	St. Petersburg
Slovakia	Site SK42106	Žilina
Slovakia	Site SK42110	Bratislava
Slovakia	Site SK42109	Kosice
Slovakia	Site SK42102	Michalovce
Slovakia	Site SK42103	Nitra
Slovakia	Site SK42101	Poprad
Slovakia	Site SK42107	Trencin
Spain	Site ES34001	Avila
Spain	Site ES34007	Barcelona
Spain	Site ES34012	Barcelona	Cataluña
Spain	Site ES34014	Barcelona	Cataluña
Spain	Site ES34004	Madrid
Spain	Site ES34019	Madrid
Spain	Site ES34020	Oviedo	Asturias
Spain	Site ES34006	Pamplona	Navarra
Spain	Site ES34010	Sabadell	Barcelona
Spain	Site ES34011	Salamanca	A Coruña
Spain	Site ES34013	Valencia	Comunidad Valenciana
Sweden	Site SE46007	Goteborg	Vastra Gotalands Lan
Sweden	Site SE46001	Malmö	Skåne Län
Sweden	Site SE46002	Örebro	Orebro Län
Sweden	Site SE46006	Stockholm	Sodermanlands Lan
Sweden	Site SE46004	Sundsvall	Vasternorrlands Lan
Taiwan	Site TW88601	Kaohsiung
Taiwan	Site TW88606	Taichung
Taiwan	Site TW88605	Taipei
Taiwan	Site TW88607	Taoyuan
United Kingdom	Site GB44002	Withington	Manchester
United States	Site US10007	Anchorage	Alaska
United States	Site US10035	Aurora	Colorado
United States	Site US10002	Burien	Washington
United States	Site US10068	Charlotte	North Carolina
United States	Site US10015	Chicago	Illinois
United States	Site US10009	Concord	North Carolina
United States	Site US10004	Dallas	Texas
United States	Site US10046	Dallas	Texas
United States	Site US10050	Denver	Colorado
United States	Site US10014	Durham	North Carolina
United States	Site US10034	Fountain Valley	California
United States	Site US10060	Greenville	North Carolina
United States	Site US10016	Homewood	Alabama
United States	Site US10045	Jeffersonville	Indiana
United States	Site US10055	Kansas City	Kansas
United States	Site US10056	La Jolla	California
United States	Site US10011	Lancaster	Pennsylvania
United States	Site US10018	Lawrenceville	New Jersey
United States	Site US10044	Middleburg Heights	Ohio
United States	Site US10012	Myrtle Beach	South Carolina
United States	Site US10059	Nashville	Tennessee
United States	Site US10025	Newburgh	New York
United States	Site US10036	Omaha	Nebraska
United States	Site US10048	Saint Petersburg	Florida
United States	Site US10026	Santa Rosa	California
United States	Site US10013	Seattle	Washington
United States	Site US10043	Springfield	Illinois
United States	Site US10029	Syracuse	New York
United States	Site US10054	Thomasville	Georgia
United States	Site US10017	Towson	Maryland
United States	Site US10008	Tucson	Arizona
United States	Site US10040	Virginia Beach	Virginia
United States	Site US10028	Wenatchee	Washington
United States	Site US10020	West Des Moines	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Chile,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Taiwan,  United Kingdom, 

References & Publications (1)

Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic Progression-Free Survival (rPFS) Based on Independent Central Review (ICR) of Bone Scan According to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Criteria	rPFS was calculated as the time from the date of randomization to the first objective evidence of radiographic progression disease (rPD) at any time or death up to 24 weeks after study drug discontinuation without documented radiographic progression, whichever occurred first. rPD was defined as progressive disease by Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan compared to baseline or week 13 according to PCWG2 criteria, as assessed by ICR or death. In participants with no rPFS event, rPFS was censored on the date of last evaluable radiographic assessment prior to the data analysis cutoff date. In participants with no baseline radiographic assessment, participants with no postbaseline radiographic assessments and participants with all postbaseline radiographic assessments documented as "not evaluable (NE)," rPFS was censored on the date of randomization.	From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Primary	rPFS Based on ICR of Bone Scan According to Protocol Assessment Criteria	rPFS was calculated as the time from the date of randomization to the first objective evidence of radiographic progression disease (rPD) at any time or death up to 24 weeks after study drug discontinuation without documented radiographic progression, whichever occurred first. rPD was defined as progressive disease by Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan compared to baseline for week 13 or the best response on treatment for week 25 or later assessments, as assessed by ICR or death. In participants with no rPFS event, rPFS was censored on the date of last evaluable radiographic assessment prior to the data analysis cutoff date. In participants with no baseline radiographic assessment, participants with no postbaseline radiographic assessments and participants with all postbaseline radiographic assessments documented as "not evaluable (NE)," rPFS was censored on the date of randomization.	From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months.
Secondary	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. In participants still alive at the date of the analysis cutoff point, OS was censored on the last date the participant was known to be alive. OS was analyzed using Kaplan-Meier estimates.	From date of randomization to OS final analysis (28 May 2021); Maximum treatment duration was 58.6 months
Secondary	Time to Prostate Specific Antigen (PSA) Progression	Time to PSA progression was calculated as the time from the date of randomization to the first observation of PSA progression. A PSA progression was defined as a = 25% increase and an absolute increase of = 2 ng/mL above the nadir, which was confirmed by a second consecutive value at least 3 weeks later. In participants with no PSA progression, time to PSA progression was censored on the date of the last PSA sample taken (or last value prior to 2 or more consecutive missed PSA assessments).	From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Time to Start of New Antineoplastic Therapy	In participants with a new antineoplastic therapy initiated for prostate cancer after randomization, time to start of a new antineoplastic therapy was defined as the time interval from randomization to the date of the first dose administration of the first antineoplastic therapy. In participants with no new antineoplastic therapy initiated for prostate cancer after randomization, time to start of new antineoplastic therapy was censored on the last visit date or the date of randomization, whichever occurred last. Time to start of new antineoplastic therapy was analyzed using Kaplan-Meier estimates.	From date of randomization to data cut-off date (28 May 2021); Maximum treatment duration was 58.6 months
Secondary	PSA Undetectable Rate	The PSA undetectable rate was defined as the percentage of participants with undetectable (< 0.2 ng/mL) PSA values at any time during study treatment, of those participants with detectable (= 0.2 ng/mL) PSA values at baseline.	Up to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Objective Response Rate (ORR)	The ORR was calculated as the percentage of participants who achieved a completed response (CR) or a partial response (PR) (unconfirmed responses) in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by ICR.	Up to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Time to Deterioration in Urinary Symptoms	In participants with deterioration, the time to deterioration was calculated as the time interval between randomization and the first deterioration in urinary symptoms at any postbaseline visit. A deterioration in urinary symptoms was defined as an increase in the Quality of Life Prostate-specific Questionnaire (QLQ-PR25) modified urinary symptoms. Subscale score by = 50% of the standard deviation observed in the QLQ-PR25 modified urinary symptoms subscale score at baseline. Modified urinary symptoms subscale score consisted of 3-items (Q31 - Q33) from the QLQ-PR25, each scored from 1 (not at all) to 4 (very much). The total modified urinary symptoms subscale score ranges from 0-100, with higher scores represents a higher level of symptomatology/problems. In participants without deterioration in urinary symptoms, the time to deterioration in urinary symptoms was censored on the date the last urinary symptoms QLQ-PR25 score was calculable.	From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Time to First Symptomatic Skeletal Event (SSE)	Time to first SSE was calculated as the time from randomization to the occurrence of the first SSE prior to the data analysis cut-off date. An SSE was defined as radiation to bone, surgery to bone, clinically apparent pathological bone fracture, or spinal cord compression. In participants with no SSE by the time of the data cut-off point, time to SSE was censored on the last visit date or the date of randomization, whichever occurred last.	From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Time to Castration Resistance	Time to castration resistance was calculated as the time from randomization to the first castration-resistant event. A castration resistance event was defined as any of the following in the presence of castrate levels of testosterone (< 50 ng/dL): radiographic disease progression, PSA progression or SSE, whichever occurred first. In participants with no documented castration resistance event, the time to castration resistance was censored on the latest date from: the date of last radiologic assessment, the last PSA sample taken prior to the start of any new prostate cancer therapy and prior to 2 or more consecutive missed PSA assessments (if applicable), and the last visit date performed.	From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Time to Deterioration of Quality of Life (QoL) in Functional Assessment of Cancer Therapy-Prostate (FACT-P)	Time to deterioration of QoL was calculated as the time interval from the date of randomization to the first date a decline from baseline of 10 points or more in the FACT-P total score was recorded. The FACT-P consists of 27 core items that assess participant function in 4 domains and 12 prostate cancer-related items grouped into 5 subscales as follows: physical wellbeing, social/family wellbeing, emotional wellbeing, functional wellbeing and prostate cancer subscale. Each item is rated on a 0 to 4 Likert-type scale. The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0 to 156), where high score represent better quality of life. In participants without FACT-P progression, the time to deterioration of QoL was censored on the date of the last FACT-P total score was calculable.	From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months
Secondary	Time to Pain Progression Based on Brief Pain Inventory-Short Form (BPI-SF)	Time to pain progression was defined as time from randomization to the first pain progression event. Pain progression was defined as an increase of = 30% from baseline in the average BPI-SF pain severity score. BPI-SF contains 9 questions with rating scales from 0 (no pain/no interference) to 10 (worst pain/interferes completely). Total score was calculated as the average of each question. Higher scores represent a higher level of pain or interference. In participants with no pain progression event, time to pain progression was censored on the last visit date where BPI-SF was collected.	From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months

External Links

•   Link to results on Astellas Clinical Study Results website