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)
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)
4 other identifiers
interventional
982
16 countries
173
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 \[gland that makes fluid that aids movement of sperm\]).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2014
Longer than P75 for phase_3
173 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2014
CompletedFirst Posted
Study publicly available on registry
October 6, 2014
CompletedStudy Start
First participant enrolled
November 26, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 19, 2018
CompletedResults Posted
Study results publicly available
August 16, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
ExpectedApril 13, 2026
April 1, 2026
3.3 years
October 2, 2014
July 21, 2021
April 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Radiographic Progression-free Survival (rPFS)
The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (\>=) 2 new lesions compared to baseline was observed in less than (\<) 12 weeks from randomization and was confirmed by a second bone scan taken \>=6 weeks later showing \>=2 additional new lesions (a total of \>=4 new lesions compared to baseline), b) the first bone scan with \>=2 new lesions compared to baseline was observed in \>=12 weeks from randomization and the new lesions were verified on the next bone scan \>=6 weeks later (a total of \>=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Up to 3 years and 4 months
Secondary Outcomes (4)
Overall Survival (OS)
Up to 5 years and 10 months
Time to Chronic Opioid Use
Up to 5 years and 10 months
Time to Initiation of Cytotoxic Chemotherapy
Up to 5 years and 10 months
Time to Pain Progression
Up to 5 years and 10 months
Study Arms (2)
Group 1: AAP and apalutamide
EXPERIMENTALParticipants will receive apalutamide 240 milligram (mg) (4\*60 mg tablets) and abiraterone acetate (AA) 1000 mg (4\*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily, until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the Open-Label Extension (OLE) or Long-Term Extension (LTE) phase (AAP + open label apalutamide or AAP alone).
Group 2: AAP and Placebo
PLACEBO COMPARATORParticipants will receive matching Placebo of apalutamide and abiraterone acetate (AA) 1000 mg (4\*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the OLE or LTE phase (AAP + open label apalutamide or AAP alone).
Interventions
Participants will receive 240 mg (4\*60 mg tablets) of apalutamide once daily orally.
Participants will receive 1000 mg (4\*250 mg tablets) of abiraterone acetate (AA) once daily orally.
Participants will receive 5 mg tablet of prednisone twice daily orally.
Participants will receive matching placebo to apalutamide once daily orally.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (173)
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Phoenix, Arizona, United States
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La Mesa, California, United States
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Los Angeles, California, United States
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Modesto, California, United States
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San Diego, California, United States
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San Francisco, California, United States
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Santa Barbara, California, United States
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Aurora, Colorado, United States
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Denver, Colorado, United States
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Jensen Beach, Florida, United States
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Lakeland, Florida, United States
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New Port Richey, Florida, United States
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Ocala, Florida, United States
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Atlanta, Georgia, United States
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Melrose, Illinois, United States
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Niles, Illinois, United States
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Marrero, Louisiana, United States
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New Orleans, Louisiana, United States
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Shreveport, Louisiana, United States
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Auburn, Maine, United States
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Baltimore, Maryland, United States
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St Louis, Missouri, United States
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Omaha, Nebraska, United States
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Las Vegas, Nevada, United States
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Albany, New York, United States
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Johnson City, New York, United States
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New York, New York, United States
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Poughkeepsie, New York, United States
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Syracuse, New York, United States
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The Bronx, New York, United States
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Columbus, Ohio, United States
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Tualatin, Oregon, United States
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Lancaster, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Charleston, South Carolina, United States
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Myrtle Beach, South Carolina, United States
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Nashville, Tennessee, United States
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Austin, Texas, United States
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Houston, Texas, United States
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Norfolk, Virginia, United States
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Richmond, Virginia, United States
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Auburn, Washington, United States
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Seattle, Washington, United States
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Spokane, Washington, United States
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Wenatchee, Washington, United States
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Madison, Wisconsin, United States
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Ciudad Automoma Buenos Aires, Argentina
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Ciudad de Buenos Aires, Argentina
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Córdoba, Argentina
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La Rioja, Argentina
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Mendoza, Argentina
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Rosario, Argentina
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Adelaide, Australia
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Ashford, Australia
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Camperdown, Australia
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Herston, Australia
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Liverpool, Australia
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Malvern, Australia
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Melbourne, Australia
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Southport, Australia
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Wahroonga, Australia
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West Heidelberg, Australia
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Woolloongabba, Australia
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Antwerp, Belgium
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Brussels, Belgium
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Ghent, Belgium
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Gosselies, Belgium
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Leuven, Belgium
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Liège, Belgium
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Namur, Belgium
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Ottignies, Belgium
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Roeselare, Belgium
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Sint-Niklaas, Belgium
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Barretos, Brazil
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Ijuí, Brazil
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Natal, Brazil
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Porto Alegre, Brazil
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São José do Rio Preto, Brazil
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São Paulo, Brazil
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Abbotsford British Columbia, British Columbia, Canada
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Kelowna, British Columbia, Canada
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Vancouver, British Columbia, Canada
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Halifax, Nova Scotia, Canada
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Barrie, Ontario, Canada
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London, Ontario, Canada
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Oakville, Ontario, Canada
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Toronto, Ontario, Canada
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Weston, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Sherbrooke, Quebec, Canada
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Angers, France
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Caen, France
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Dijon, France
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Le Mans, France
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Lyon, France
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Montpellier, France
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Paris, France
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Saint-Herblain, France
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Toulouse, France
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Berlin, Germany
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Dresden, Germany
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Freiburg im Breisgau, Germany
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Hamburg, Germany
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Heidelberg, Germany
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Münster, Germany
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Nürtingen, Germany
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Wuppertal, Germany
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Fukuoka, Japan
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Kanazawa, Japan
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Kashiwa, Japan
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Kita-Gun, Japan
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Kumamoto, Japan
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Kurume, Japan
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Matsuyama, Japan
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Miyazaki, Japan
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Nagasaki, Japan
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Osaka, Japan
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Ōsaka-sayama, Japan
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Sakura, Japan
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Sapporo, Japan
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Ube, Japan
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Yokohama, Japan
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Chihuahua City, Mexico
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Cuernavaca, Mexico
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Culiacán, Mexico
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México, Mexico
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Oaxaca City, Mexico
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Zapopan, Mexico
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Amsterdam, Netherlands
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Amsterdam-Zuidoost, Netherlands
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Blaricum, Netherlands
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Dordrecht, Netherlands
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Groningen, Netherlands
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Heerlen, Netherlands
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Nieuwegein, Netherlands
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Nijmegen, Netherlands
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Rotterdam, Netherlands
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The Hague, Netherlands
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Kursk, Russia
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Moscow, Russia
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Omsk, Russia
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Pyatigorsk, Russia
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Rostov-on-Don, Russia
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Saint Petersburg, Russia
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Ufa, Russia
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Bloemfontein, South Africa
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Cape Town, South Africa
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Johannesburg, South Africa
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Pretoria, South Africa
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Goyang-si, South Korea
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Seongnam, South Korea
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Seoul, South Korea
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Alcorcón, Spain
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Barcelona, Spain
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Cadiz, Spain
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Córdoba, Spain
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Madrid, Spain
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San Sebastián de los Reyes, Spain
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Valencia, Spain
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Ayr, United Kingdom
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Belfast, United Kingdom
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Birmingham, United Kingdom
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Edinburgh, United Kingdom
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Glasgow, United Kingdom
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London, United Kingdom
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Manchester, United Kingdom
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Metropolitan Borough of Wirral, United Kingdom
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Plymouth, United Kingdom
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Preston, United Kingdom
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Stevenage, United Kingdom
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Sutton, United Kingdom
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Westcliff-on-Sea, United Kingdom
Related Publications (2)
Roy S, Wallis CJD, Morgan SC, Kishan AU, Le ATT, Malone J, Sun Y, Spratt DE, Saad F, Malone S. Implications of metastatic stage at presentation in docetaxel naive metastatic castrate resistant prostate cancer. Prostate. 2023 Jul;83(10):912-921. doi: 10.1002/pros.24512. Epub 2023 Apr 18.
PMID: 37071764DERIVEDSaad 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.
PMID: 34600602DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
This study used an electronic handheld device to collect responses for patient-reported outcome (PRO) questionnaires, which might have resulted in a lower-than-expected compliance due to unfamiliarity of the elderly population with the device.
Results Point of Contact
- Title
- Executive Medical Director
- Organization
- Aragon Pharmaceuticals, Inc.
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 2, 2014
First Posted
October 6, 2014
Study Start
November 26, 2014
Primary Completion
March 19, 2018
Study Completion (Estimated)
December 31, 2027
Last Updated
April 13, 2026
Results First Posted
August 16, 2021
Record last verified: 2026-04