Clinical trial NCT02257736: An Efficacy and Safety Study of Apalutamide (JNJ-56021927) in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)
Official title: A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostatic Neoplasms
Keywords: Prostatic neoplasms
JN56021927
ZYTIGA
Prednisone
Abiraterone acetate
Apalutamide
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-06
Enrollment: 982
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the radiographic progression-free survival (rPFS) of apalutamide in combination with abiraterone acetate (AA) plus prednisone or prednisolone (AAP) and AAP in participants with chemotherapy-naive (participants who did not receive any chemotherapy \[treatment of cancer using drugs\]) metastatic castration-resistant prostate cancer (mCRPC) (cancer of prostate gland \[gland that makes fluid that aids movement of sperm\]).

Detailed description: This is a randomized (study drug assigned by chance), double-blind (neither the Investigator nor the participant know the treatment) placebo-controlled and multicenter (when more than 1 hospital or medical school team work on a medical research study) study to determine if participants with chemotherapy-naive mCRPC will benefit from the addition of apalutamide to AAP compared with AAP alone. The study consists of 3 phases: Screening phase; Treatment phase, and Follow-up phase. At the final analysis, the study will be unblinded. After the Independent Data Monitoring Committee (IDMC) review and the sponsor's subsequent decision participants will be offered to receive treatment either in the Open-Label Extension Phase or the Long-Term Extension Phase of study. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Adenocarcinoma of the prostate
* Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans (visceral or lymph node disease). If lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to (\>=) 2 centimeter (cm) in the longest diameter
* Castration-resistant prostate cancer demonstrated during continuous androgen deprivation therapy (ADT), defined as 3 rises of PSA, at least 1 week apart with the last androgen deprivation therapy (PSA) \>= 2 nanogram per milliliters (ng/mL)
* Participants who received a first generation anti-androgen (eg, bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after the washout period
* Prostate cancer progression documented by prostate-specific antigen (PSA) according to the Prostate Cancer Clinical Trials Working Group (PCWG2) or radiographic progression of soft tissue according to modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) modified based on PCWG2, or radiographic progression of bone according to PCWG2
* Participants who cross-over from Prednisone alone to open-label apalutamide plus AAP should still be in the double-blind phase of the study, should be receiving AAP alone and should have ECOG 0-1-2.

Exclusion Criteria:

* Small cell or neuroendocrine carcinoma of the prostate
* Known brain metastases
* Prior chemotherapy for prostate cancer, except if administered in the adjuvant/neoadjuvant setting
* Previously treated with ketoconazole for prostate cancer for greater than 7 days
* Therapies that must be discontinued or substituted at least 4 weeks prior to randomization include the following: a) Medications known to lower the seizure threshold, b) Herbal and non-herbal products that may decrease PSA levels (example \[eg\], saw palmetto, pomegranate) or c) Any investigational agent
* At Screening need for parenteral or oral opioid analgesics (eg, codeine, dextropropoxyphene)

Primary outcomes:
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: Up to 3 years and 4 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 5 years and 10 months
measure: Time to Chronic Opioid Use
timeFrame: Up to 5 years and 10 months
measure: Time to Initiation of Cytotoxic Chemotherapy
timeFrame: Up to 5 years and 10 months
measure: Time to Pain Progression
timeFrame: Up to 5 years and 10 months
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: La Mesa
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Modesto
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Jensen Beach
country: United States
state: Florida
city: Lakeland
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Melrose
country: United States
state: Illinois
city: Niles
country: United States
state: Illinois
city: Marrero
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Auburn
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Albany
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: Johnson City
country: United States
state: New York
city: New York
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state: New York
city: Poughkeepsie
country: United States
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city: Syracuse
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city: Columbus
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state: Ohio
city: Tualatin
country: United States
state: Oregon
city: Lancaster
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
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state: South Carolina
city: Myrtle Beach
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state: South Carolina
city: Nashville
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state: Tennessee
city: Austin
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state: Texas
city: Houston
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state: Texas
city: Norfolk
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state: Virginia
city: Richmond
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state: Virginia
city: Auburn
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state: Washington
city: Seattle
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city: Spokane
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state: Washington
city: Wenatchee
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state: Washington
city: Madison
country: United States
state: Wisconsin
city: Ciudad Automoma Buenos Aires
country: Argentina
city: Ciudad de Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Rioja
country: Argentina
city: Mendoza
country: Argentina
city: Rosario
country: Argentina
city: Adelaide
country: Australia
city: Ashford
country: Australia
city: Camperdown
country: Australia
city: Herston
country: Australia
city: Liverpool
country: Australia
city: Malvern
country: Australia
city: Melbourne
country: Australia
city: Southport
country: Australia
city: Wahroonga
country: Australia
city: West Heidelberg
country: Australia
city: Woolloongabba
country: Australia
city: Antwerpen
country: Belgium
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Gosselies
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Namur
country: Belgium
city: Ottignies
country: Belgium
city: Roeselare
country: Belgium
city: Sint-Niklaas
country: Belgium
city: Barretos
country: Brazil
city: Ijui
country: Brazil
city: Natal
country: Brazil
city: Porto Alegre
country: Brazil
city: Sao Jose do Rio Preto
country: Brazil
city: Sao Paulo
country: Brazil
city: Abbotsford
country: Canada
state: British Columbia
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Barrie
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Weston
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Angers Cedex 9
country: France
city: Caen Cedex 05
country: France
city: Dijon Cedex
country: France
city: Le Mans Cedex 2
country: France
city: Lyon cedex 03
country: France
city: Lyon
country: France
city: Montpellier
country: France
city: Paris Cedex 15
country: France
city: Saint Herblain
country: France
city: Toulouse Cedex 9
country: France
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Muenster
country: Germany
city: Nuertingen
country: Germany
city: Wuppertal
country: Germany
city: Fukuoka-shi
country: Japan
city: Kanazawa
country: Japan
city: Kashiwa
country: Japan
city: Kita-Gun
country: Japan
city: Kumamoto
country: Japan
city: Kurume
country: Japan
city: Matsuyama-Shi
country: Japan
city: Miyazaki
country: Japan
city: Nagasaki
country: Japan
city: Osaka-Sayama
country: Japan
city: Osaka
country: Japan
city: Sakura
country: Japan
city: Sapporo
country: Japan
city: Ube
country: Japan
city: Yokohama
country: Japan
city: Goyang-Si
country: Korea, Republic of
city: Seongnam
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Chihuahua
country: Mexico
city: Cuernavaca
country: Mexico
city: Culiacan
country: Mexico
city: Mexico
country: Mexico
city: Oaxaca
country: Mexico
city: Zapopan
country: Mexico
city: Amsterdam Zuidoost
country: Netherlands
city: Amsterdam
country: Netherlands
city: Blaricum
country: Netherlands
city: Den Haag
country: Netherlands
city: Dordrecht
country: Netherlands
city: Groningen
country: Netherlands
city: Heerlen
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Kursk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Omsk
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Rostov-on-Don
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria
country: South Africa
city: Alcorcon
country: Spain
city: Barcelona
country: Spain
city: Cadiz
country: Spain
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: San Sebastián de los Reyes
country: Spain
city: Valencia
country: Spain
city: Ayr
country: United Kingdom
city: Belfast
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Preston
country: United Kingdom
city: Stevenage
country: United Kingdom
city: Sutton
country: United Kingdom
city: Westcliff on Sea
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021 Nov;22(11):1541-1559. doi: 10.1016/S1470-2045(21)00402-2. Epub 2021 Sep 30.