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)

• ClinicalTrials.gov Identifier: NCT02257736
• Recruitment Status: Active, not recruiting
• First Posted: October 6, 2014
• Results First Posted: August 16, 2021
• Last Update Posted: April 25, 2024
• Sponsor: Aragon Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Aragon Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: October 2, 2014
• First Posted Date: October 6, 2014
• Results First Submitted Date: July 21, 2021
• Results First Posted Date: August 16, 2021
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: November 26, 2014
• Actual Primary Completion Date: March 19, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2021)

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.

Original Primary Outcome Measures (submitted: October 2, 2014)

Radiographic Progression-free Survival (rPFS). [ Time Frame: Time from randomization until death or lost to follow-up or withdrawal of consent or study termination, whichever occurs first, up to 5 years ]

Radiographic progression is determined if there are more than or equal (>=) to 2 lesions in less than (<) 12 weeks from randomization and there are 2 new lesions when observed 6 weeks later or, >= 2 lesions after 12 weeks and the same is confirmed 6 weeks later or, progression of soft tissue lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Current Secondary Outcome Measures (submitted: July 21, 2021)

• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: October 2, 2014)

• Overall Survival (OS) [ Time Frame: Time from randomization until death or lost to follow-up or withdrawal of consent or study termination, whichever occurs first, up to 5 years ]
  The OS is defined as the time from randomization to date of death from any cause.
• Time to Chronic Opioid Use [ Time Frame: Baseline up to 5 years ]
  Time to chronic opioid use is defined as the time from date of randomization to the first date of opioid use.
• Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Baseline up to 5 years ]
  Time to initiation of cytotoxic chemotherapy is defined as the time from date of randomization to the date of initiation of cytotoxic chemotherapy.
• Time to Pain Progression [ Time Frame: Baseline up to 5 years ]
  Time to pain progression is defined as time from randomization to progression in worst pain over the last 24 hours (item 3) in the Brief pain inventory-short form (BPI-SF). BPI-SF is a self-evaluated pain assessment form consisting of 15 items. The Worst Pain-item 3 of the BPI-SF scale is used to assess pain on 11-point Likert scale which has range: 0 (no pain) to 10 (pain as bad as you can imagine).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Prostatic Neoplasms

Intervention

• 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.
• Drug: Placebo
  Participants will receive matching placebo to apalutamide once daily orally.

Study Arms

• 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).
  Interventions:

  • Drug: Apalutamide
  • Drug: Abiraterone acetate
  • Drug: Prednisone
• 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).
  Interventions:

  • Drug: Abiraterone acetate
  • Drug: Prednisone
  • Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 21, 2021): 982
• Original Estimated Enrollment (submitted: October 2, 2014): 960
• Estimated Study Completion Date: December 31, 2025
• Actual Primary Completion Date: March 19, 2018 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Japan, Korea, Republic of, Mexico, Netherlands, Russian Federation, South Africa, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT02257736
• Other Study ID Numbers: CR105505; 56021927PCR3001 ( Other Identifier: Janssen Research & Development, LLC ); 2014-001718-25 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Aragon Pharmaceuticals, Inc.
• Original Responsible Party: Janssen Research & Development, LLC
• Current Study Sponsor: Aragon Pharmaceuticals, Inc.
• Original Study Sponsor: Janssen Research & Development, LLC
• Collaborators: Not Provided

Investigators

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

• PRS Account: Aragon Pharmaceuticals, Inc.
• Verification Date: April 2024