Back to resultsAn 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)
Primary Purpose
Prostatic Neoplasms
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Apalutamide
Abiraterone acetate
Prednisone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasms focused on measuring Prostatic neoplasms, JN56021927, ZYTIGA, Prednisone, Abiraterone acetate, Apalutamide
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group 1: AAP and apalutamide
Group 2: AAP and Placebo
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Overall Survival (OS)
The OS was defined as the time from randomization to date of death from any cause.
Time to Chronic Opioid Use
Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.
Time to Initiation of Cytotoxic Chemotherapy
Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
Time to Pain Progression
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.
Full Information
NCT ID
NCT02257736
First Posted
October 2, 2014
Last Updated
October 10, 2023
Sponsor
Aragon Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02257736
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 26, 2014 (Actual)
Primary Completion Date
March 19, 2018 (Actual)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aragon Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms
Keywords
Prostatic neoplasms, JN56021927, ZYTIGA, Prednisone, Abiraterone acetate, Apalutamide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
982 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: AAP and apalutamide
Arm Type
Experimental
Arm Description
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).
Arm Title
Group 2: AAP and Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Apalutamide
Intervention Description
Participants will receive 240 mg (4*60 mg tablets) of apalutamide once daily orally.
Intervention Type
Drug
Intervention Name(s)
Abiraterone acetate
Other Intervention Name(s)
ZYTIGA
Intervention Description
Participants will receive 1000 mg (4*250 mg tablets) of abiraterone acetate (AA) once daily orally.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Participants will receive 5 mg tablet of prednisone twice daily orally.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching placebo to apalutamide once daily orally.
Primary Outcome Measure Information:
Title
Radiographic Progression-free Survival (rPFS)
Description
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.
Time Frame
Up to 3 years and 4 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
The OS was defined as the time from randomization to date of death from any cause.
Time Frame
Up to 5 years and 10 months
Title
Time to Chronic Opioid Use
Description
Time to chronic opioid use was defined as the time from date of randomization to the first date of opioid use.
Time Frame
Up to 5 years and 10 months
Title
Time to Initiation of Cytotoxic Chemotherapy
Description
Time to initiation of cytotoxic chemotherapy was defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
Time Frame
Up to 5 years and 10 months
Title
Time to Pain Progression
Description
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.
Time Frame
Up to 5 years and 10 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
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Phoenix
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Lyon
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Paris Cedex 15
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France
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France
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France
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Germany
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Germany
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Japan
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Dordrecht
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Netherlands
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Kursk
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Moscow
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Russian Federation
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Pyatigorsk
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Russian Federation
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Rostov-on-Don
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saint-Petersburg,
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Russian Federation
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Saint-Petersburg
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Ufa
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Bloemfontein
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Stevenage
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Sutton
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Westcliff on Sea
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United Kingdom
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Wirral
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United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
34600602
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.
Results Reference
derived
Learn more about this trial
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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