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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)

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ClinicalTrials.gov Identifier: NCT02257736
Recruitment Status : Active, not recruiting
First Posted : October 6, 2014
Results First Posted : August 16, 2021
Last Update Posted : August 20, 2021
Sponsor:
Information provided by (Responsible Party):
Aragon Pharmaceuticals, Inc.

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]).

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: Apalutamide Drug: Abiraterone acetate Drug: Prednisone Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 982 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 26, 2014
Actual Primary Completion Date : March 19, 2018
Estimated Study Completion Date : August 24, 2021

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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.




Primary Outcome Measures :
  1. Radiographic Progression-free Survival (rPFS) [ Time Frame: Up to 5 years and 10 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02257736


Locations
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Sponsors and Collaborators
Aragon Pharmaceuticals, Inc.
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Aragon Pharmaceuticals, Inc.:
Study Protocol  [PDF] April 14, 2020
Statistical Analysis Plan  [PDF] September 21, 2020

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Responsible Party: Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02257736    
Other Study ID Numbers: CR105505
56021927PCR3001 ( Other Identifier: Janssen Research & Development, LLC )
2014-001718-25 ( EudraCT Number )
First Posted: October 6, 2014    Key Record Dates
Results First Posted: August 16, 2021
Last Update Posted: August 20, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Aragon Pharmaceuticals, Inc.:
Prostatic neoplasms
JN56021927
ZYTIGA
Prednisone
Abiraterone acetate
Apalutamide
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Prednisone
Abiraterone Acetate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors