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)

March 26, 2024 updated by: Aragon Pharmaceuticals, Inc.

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)

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]).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

982

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Ciudad Automoma Buenos Aires, Argentina
      • Ciudad de Buenos Aires, Argentina
      • Cordoba, Argentina
      • La Rioja, Argentina
      • Mendoza, Argentina
      • Rosario, Argentina
  • Australia
      • Adelaide, Australia
      • Ashford, Australia
      • Camperdown, Australia
      • Herston, Australia
      • Liverpool, Australia
      • Malvern, Australia
      • Melbourne, Australia
      • Southport, Australia
      • Wahroonga, Australia
      • West Heidelberg, Australia
      • Woolloongabba, Australia
  • Belgium
      • Antwerpen, Belgium
      • Bruxelles, Belgium
      • Gent, Belgium
      • Gosselies, Belgium
      • Leuven, Belgium
      • Liege, Belgium
      • Namur, Belgium
      • Ottignies, Belgium
      • Roeselare, Belgium
      • Sint-Niklaas, Belgium
  • Brazil
      • Barretos, Brazil
      • Ijui, Brazil
      • Natal, Brazil
      • Porto Alegre, Brazil
      • Sao Jose do Rio Preto, Brazil
      • Sao Paulo, Brazil
  • Canada
      • Quebec, Canada
    • British Columbia
      • Abbotsford, British Columbia, Canada
      • Kelowna, British Columbia, Canada
      • Vancouver, British Columbia, Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
    • Ontario
      • Barrie, Ontario, Canada
      • London, Ontario, Canada
      • Oakville, Ontario, Canada
      • Toronto, Ontario, Canada
      • Weston, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
      • Sherbrooke, Quebec, Canada
  • France
      • Angers Cedex 9, France
      • Caen Cedex 05, France
      • Dijon Cedex, France
      • Le Mans Cedex 2, France
      • Lyon, France
      • Lyon cedex 03, France
      • Montpellier, France
      • Paris Cedex 15, France
      • Saint Herblain, France
      • Toulouse Cedex 9, France
  • Germany
      • Berlin, Germany
      • Dresden, Germany
      • Freiburg, Germany
      • Hamburg, Germany
      • Heidelberg, Germany
      • Muenster, Germany
      • Nuertingen, Germany
      • Wuppertal, Germany
  • Japan
      • Fukuoka-shi, Japan
      • Kanazawa, Japan
      • Kashiwa, Japan
      • Kita-Gun, Japan
      • Kumamoto, Japan
      • Kurume, Japan
      • Matsuyama-Shi, Japan
      • Miyazaki, Japan
      • Nagasaki, Japan
      • Osaka, Japan
      • Osaka-Sayama, Japan
      • Sakura, Japan
      • Sapporo, Japan
      • Ube, Japan
      • Yokohama, Japan
  • Korea, Republic of
      • Goyang-Si, Korea, Republic of
      • Seongnam, Korea, Republic of
      • Seoul, Korea, Republic of
  • Mexico
      • Chihuahua, Mexico
      • Cuernavaca, Mexico
      • Culiacan, Mexico
      • Mexico, Mexico
      • Oaxaca, Mexico
      • Zapopan, Mexico
  • Netherlands
      • Amsterdam, Netherlands
      • Amsterdam Zuidoost, Netherlands
      • Blaricum, Netherlands
      • Den Haag, Netherlands
      • Dordrecht, Netherlands
      • Groningen, Netherlands
      • Heerlen, Netherlands
      • Nieuwegein, Netherlands
      • Nijmegen, Netherlands
      • Rotterdam, Netherlands
  • Russian Federation
      • Kursk, Russian Federation
      • Moscow, Russian Federation
      • Omsk, Russian Federation
      • Pyatigorsk, Russian Federation
      • Rostov-on-Don, Russian Federation
      • Saint Petersburg, Russian Federation
      • Saint-Petersburg, Russian Federation
      • Saint-Petersburg,, Russian Federation
      • Ufa, Russian Federation
  • South Africa
      • Bloemfontein, South Africa
      • Cape Town, South Africa
      • Johannesburg, South Africa
      • Pretoria, South Africa
  • Spain
      • Alcorcon, Spain
      • Barcelona, Spain
      • Cadiz, Spain
      • Cordoba, Spain
      • Madrid, Spain
      • San Sebastián de los Reyes, Spain
      • Valencia, Spain
  • United Kingdom
      • Ayr, United Kingdom
      • Belfast, United Kingdom
      • Birmingham, United Kingdom
      • Edinburgh, United Kingdom
      • Glasgow, United Kingdom
      • London, United Kingdom
      • Manchester, United Kingdom
      • Plymouth, United Kingdom
      • Preston, United Kingdom
      • Stevenage, United Kingdom
      • Sutton, United Kingdom
      • Westcliff on Sea, United Kingdom
      • Wirral, United Kingdom
  • United States
    • Arizona
      • Phoenix, Arizona, United States
    • California
      • La Mesa, California, United States
      • Los Angeles, California, United States
      • Modesto, California, United States
      • San Diego, California, United States
      • San Francisco, California, United States
      • Santa Barbara, California, United States
    • Colorado
      • Aurora, Colorado, United States
      • Denver, Colorado, United States
    • Florida
      • Jensen Beach, Florida, United States
      • Lakeland, Florida, United States
      • New Port Richey, Florida, United States
      • Ocala, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Illinois
      • Melrose, Illinois, United States
      • Niles, Illinois, United States
    • Louisiana
      • Marrero, Louisiana, United States
      • New Orleans, Louisiana, United States
      • Shreveport, Louisiana, United States
    • Maine
      • Auburn, Maine, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • Nevada
      • Las Vegas, Nevada, United States
    • New York
      • Albany, New York, United States
      • Bronx, New York, United States
      • Johnson City, New York, United States
      • New York, New York, United States
      • Poughkeepsie, New York, United States
      • Syracuse, New York, United States
    • Ohio
      • Columbus, Ohio, United States
    • Oregon
      • Tualatin, Oregon, United States
    • Pennsylvania
      • Lancaster, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
      • Myrtle Beach, South Carolina, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Austin, Texas, United States
      • Houston, Texas, United States
    • Virginia
      • Norfolk, Virginia, United States
      • Richmond, Virginia, United States
    • Washington
      • Auburn, Washington, United States
      • Seattle, Washington, United States
      • Spokane, Washington, United States
      • Wenatchee, Washington, United States
    • Wisconsin
      • Madison, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: Apalutamide
Participants will receive 240 mg (4*60 mg tablets) of apalutamide once daily orally.
Drug: Abiraterone acetate
Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.
Other Names:
  • ZYTIGA
Drug: Prednisone
Participants will receive 5 mg tablet of prednisone twice daily orally.
Placebo Comparator: 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).
Drug: Abiraterone acetate
Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.
Other Names:
  • ZYTIGA
Drug: Prednisone
Participants will receive 5 mg tablet of prednisone twice daily orally.
Drug: Placebo
Participants will receive matching placebo to apalutamide once daily orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic Progression-free Survival (rPFS)
Time Frame: Up to 3 years and 4 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 5 years and 10 months
The OS was defined as the time from randomization to date of death from any cause.
Up to 5 years and 10 months
Time to Chronic Opioid Use
Time Frame: Up to 5 years and 10 months
Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.
Up to 5 years and 10 months
Time to Initiation of Cytotoxic Chemotherapy
Time Frame: Up to 5 years and 10 months
Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
Up to 5 years and 10 months
Time to Pain Progression
Time Frame: Up to 5 years and 10 months
Time to pain progression: time from randomization to first date that participant either experienced an increase by 2 points from baseline in Brief Pain Inventory Short Form (BPI-SF) worst pain intensity item (item 3) or Case Report Form (CRF) pain, observed at 2 consecutive evaluations >=4 wks apart, or initiation of chronic opioids as defined in time to chronic opioid use, whichever occurred first. BPI-SF is a self-administered questionnaire developed to assess severity of pain and impact of pain on daily functions. Item 3(worst pain intensity) asks participants to rate worst pain in prior 7-days on a 0-10 numeric rating scale, where "0" indicates "No pain" and "10" indicates "Pain as bad as you can imagine." A lower score is better.CRF pain refers to participant's response to global pain assessment "How would you rate your pain over the past 7 days?"with a scale of 0("No pain") to 10("Pain as bad as you can imagine"),that is systematically reported and recorded on the eCRF.
Up to 5 years and 10 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aragon Pharmaceuticals, Inc.

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 26, 2014

Primary Completion (Actual)

March 19, 2018

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 2, 2014

First Submitted That Met QC Criteria

October 2, 2014

First Posted (Estimated)

October 6, 2014

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR105505
  • 56021927PCR3001 (Other Identifier: Janssen Research & Development, LLC)
  • 2014-001718-25 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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