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)

NCT ID: NCT02257736

Last Updated: 2025-11-12

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

982 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-26

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Prostatic Neoplasms

Keywords

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Prostatic neoplasms JN56021927 ZYTIGA Prednisone Abiraterone acetate Apalutamide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Group 1: AAP and apalutamide

Participants 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 Type EXPERIMENTAL

Apalutamide

Intervention Type DRUG

Participants will receive 240 mg (4\*60 mg tablets) of apalutamide once daily orally.

Abiraterone acetate

Intervention Type DRUG

Participants will receive 1000 mg (4\*250 mg tablets) of abiraterone acetate (AA) once daily orally.

Prednisone

Intervention Type DRUG

Participants will receive 5 mg tablet of prednisone twice daily orally.

Group 2: AAP and Placebo

Participants 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).

Group Type PLACEBO_COMPARATOR

Abiraterone acetate

Intervention Type DRUG

Participants will receive 1000 mg (4\*250 mg tablets) of abiraterone acetate (AA) once daily orally.

Prednisone

Intervention Type DRUG

Participants will receive 5 mg tablet of prednisone twice daily orally.

Placebo

Intervention Type DRUG

Participants will receive matching placebo to apalutamide once daily orally.

Interventions

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Apalutamide

Participants will receive 240 mg (4\*60 mg tablets) of apalutamide once daily orally.

Intervention Type DRUG

Abiraterone acetate

Participants will receive 1000 mg (4\*250 mg tablets) of abiraterone acetate (AA) once daily orally.

Intervention Type DRUG

Prednisone

Participants will receive 5 mg tablet of prednisone twice daily orally.

Intervention Type DRUG

Placebo

Participants will receive matching placebo to apalutamide once daily orally.

Intervention Type DRUG

Other Intervention Names

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ZYTIGA

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Aragon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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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, 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

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Countries

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United States Argentina Australia Belgium Brazil Canada France Germany Japan Mexico Netherlands Russia South Africa South Korea Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37071764 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34600602 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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56021927PCR3001

Identifier Type: OTHER

Identifier Source: secondary_id

2014-001718-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-508606-26-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR105505

Identifier Type: -

Identifier Source: org_study_id