Prostatic Neoplasms
Conditions
Keywords
Prostatic neoplasms, JN56021927, ZYTIGA, Prednisone, Abiraterone acetate, Apalutamide
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.
Interventions
DRUGApalutamide
Participants will receive 240 mg (4\*60 mg tablets) of apalutamide once daily orally.
DRUGAbiraterone acetate
Participants will receive 1000 mg (4\*250 mg tablets) of abiraterone acetate (AA) once daily orally.
DRUGPrednisone
Participants will receive 5 mg tablet of prednisone twice daily orally.
DRUGPlacebo
Participants will receive matching placebo to apalutamide once daily orally.
Sponsors
Aragon Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-free Survival (rPFS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 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 | 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 | 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 | 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. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, France, Germany, Japan, Mexico, Netherlands, Russia, South Africa, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Treatment disposition has been reported in participant flow.
Participants by arm
| Arm | Count |
|---|---|
| Placebo+ Abiraterone Acetate - Prednisolone Participants received 4\*60 milligrams (mg) tablets of matching placebo orally once daily (qd) with or without food and 4\*250 mg tablets of abiraterone acetate (AA) orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles (each cycle was equal to 28 days), and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. | 490 |
| Apalutamide + Abiraterone Acetate - Prednisolone Participants received 4\*60 mg tablets of apalutamide tablets orally qd with or without food and 4\*250 mg tablets of AA orally qd on empty stomach followed by prednisolone 5 mg orally twice daily with food for 24 cycles, and thereafter every 3 cycles. Participants received treatment until radiographic progression or unequivocal clinical progression, unacceptable toxicity, or death. | 492 |
| Total | 982 |
Baseline characteristics
| Characteristic | Placebo+ Abiraterone Acetate - Prednisolone | Total | Apalutamide + Abiraterone Acetate - Prednisolone |
|---|---|---|---|
| Age, Continuous | 70.7 years STANDARD_DEVIATION 8.06 | 71.1 years STANDARD_DEVIATION 8.21 | 71.4 years STANDARD_DEVIATION 8.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 54 Participants | 104 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 411 Participants | 833 Participants | 422 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 25 Participants | 45 Participants | 20 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 8 Participants | 17 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 53 Participants | 111 Participants | 58 Participants |
| Race/Ethnicity, Customized Black or African American | 18 Participants | 37 Participants | 19 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 18 Participants | 39 Participants | 21 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 20 Participants | 40 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 373 Participants | 738 Participants | 365 Participants |
| Region of Enrollment ARGENTINA | 3 Participants | 6 Participants | 3 Participants |
| Region of Enrollment AUSTRALIA | 31 Participants | 78 Participants | 47 Participants |
| Region of Enrollment BELGIUM | 16 Participants | 32 Participants | 16 Participants |
| Region of Enrollment BRAZIL | 21 Participants | 39 Participants | 18 Participants |
| Region of Enrollment CANADA | 12 Participants | 30 Participants | 18 Participants |
| Region of Enrollment FRANCE | 18 Participants | 34 Participants | 16 Participants |
| Region of Enrollment GERMANY | 10 Participants | 19 Participants | 9 Participants |
| Region of Enrollment ITALY | 33 Participants | 69 Participants | 36 Participants |
| Region of Enrollment JAPAN | 23 Participants | 50 Participants | 27 Participants |
| Region of Enrollment MEXICO | 19 Participants | 35 Participants | 16 Participants |
| Region of Enrollment NETHERLANDS | 14 Participants | 30 Participants | 16 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 59 Participants | 105 Participants | 46 Participants |
| Region of Enrollment SOUTH AFRICA | 9 Participants | 17 Participants | 8 Participants |
| Region of Enrollment SOUTH KOREA | 28 Participants | 57 Participants | 29 Participants |
| Region of Enrollment SPAIN | 43 Participants | 79 Participants | 36 Participants |
| Region of Enrollment UNITED KINGDOM | 23 Participants | 50 Participants | 27 Participants |
| Region of Enrollment UNITED STATES | 128 Participants | 252 Participants | 124 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 490 Participants | 982 Participants | 492 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 350 / 489 | 338 / 490 |
| other Total, other adverse events | 459 / 489 | 472 / 490 |
| serious Total, serious adverse events | 166 / 489 | 192 / 490 |
Outcome results
Primary
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.
Time frame: Up to 3 years and 4 months
Population: Intent-to-treat (ITT) population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+ Abiraterone Acetate - Prednisolone | Radiographic Progression-free Survival (rPFS) | 16.59 months |
| Apalutamide + Abiraterone Acetate - Prednisolone | Radiographic Progression-free Survival (rPFS) | 23.98 months |
Secondary
Overall Survival (OS)
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
Population: ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+ Abiraterone Acetate - Prednisolone | Overall Survival (OS) | 33.71 months |
| Apalutamide + Abiraterone Acetate - Prednisolone | Overall Survival (OS) | 36.17 months |
Secondary
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 frame: Up to 5 years and 10 months
Population: ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+ Abiraterone Acetate - Prednisolone | Time to Chronic Opioid Use | 53.26 months |
| Apalutamide + Abiraterone Acetate - Prednisolone | Time to Chronic Opioid Use | 46.98 months |
Secondary
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 frame: Up to 5 years and 10 months
Population: ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+ Abiraterone Acetate - Prednisolone | Time to Initiation of Cytotoxic Chemotherapy | 34.23 months |
| Apalutamide + Abiraterone Acetate - Prednisolone | Time to Initiation of Cytotoxic Chemotherapy | 36.11 months |
Secondary
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.
Time frame: Up to 5 years and 10 months
Population: ITT population included all randomized participants who were classified according to their assigned treatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo+ Abiraterone Acetate - Prednisolone | Time to Pain Progression | 26.51 months |
| Apalutamide + Abiraterone Acetate - Prednisolone | Time to Pain Progression | 21.82 months |