Prostatic Neoplasms
Conditions
Keywords
Prostatic neoplasms, Diethylstilbestrol therapy, Abiraterone acetate, Prednisone, Androgen deprivation therapy
Brief summary
The purpose of this study is to evaluate the efficacy, based on prostate-specific antigen (PSA) progression, of abiraterone acetate in participants with metastatic (spread of cancer cells from one part of the body to another) castration (any action, surgical, chemical, or otherwise, by which a male loses the functions of the testes) resistant prostate cancer (cancer in prostrate; a gland that makes fluid that aids movement of sperm) (mCRPC), chemo-naive (treatment of cancer is not done using drugs), who received a prior diethylstilbestrol therapy (DES).
Detailed description
This is a Phase 2, multinational (when medical research study takes place in more than one country), multicenter (when more than one hospital or medical school team work on a medical research study), open-label (all people know the identity of the intervention), and single arm study to determine benefits of abiraterone acetate and low-dose prednisone to androgen deprivation therapy (ADT) in mCRPC participants who failed to prior DES therapy. The study will consist of a Screening Phase of up to 28 days before enrollment; a PSA Evaluation Phase; and a Follow-up Phase of up to 24 months. Each cycle of abiraterone therapy will be of 28 days. Participants will receive 1000 milligram (mg) abiraterone acetate orally once daily plus prednisone 5 mg orally once daily plus stable regimen of ADT (luteinizing hormone-releasing hormone \[LHRH\] agonists) as per Investigator's discretion. Treatment will continue until PSA progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity. Efficacy will primarily be assessed by time to PSA progression. Participants' safety will be monitored throughout the study.
Interventions
DRUGAbiraterone acetate
Participants will receive abiraterone acetate 1000 mg (4\*250 mg tablets) orally once daily until PSA progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
DRUGPrednisone
Participants will prednisone 5 mg orally once daily from Day 1 of Cycle 1 and continues until PSA progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity.
DRUGAndrogen deprivation therapy (ADT)
Participants will remain on a stable regimen of ADT, that is, luteinizing hormone-releasing hormone (LHRH) agonists including leuprolide acetate and goserelin acetate as per Investigator's discretion.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology * Prior therapy with diethylstilbestrol (DES) for castration resistant prostate cancer. Participants should demonstrate evidence of progression on DES or evidence of grades 3/4 toxicities on DES * Metastatic disease documented by positive bone scan or metastatic lesions on computerized tomography (CT) or magnetic resonance imaging (MRI) * May have received prior androgen blockage (bicalutamide or flutamide) but must have been discontinued for least 28 days * Ongoing androgen deprivation therapy (ADT) (luteinizing hormone-releasing hormone \[LHRH\] agonist or orchiectomy), with serum testosterone level of less than 50 nanogram per deciliter (1.7 nanomole per liter) and eligible participants must maintain ADT
Exclusion criteria
* Active infection or other medical condition that would make prednisone use contraindicated * Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 milligram (mg) prednisone per day * Pathological finding consistent with small cell carcinoma of the prostate * Known brain metastasis * Has had prior cytotoxic chemotherapy or biologic therapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Prostate-specific Antigen (PSA) Progression | Up to 2 years | Time to PSA progression was calculated from date of enrollment to the date of first documentation of PSA progression. As per Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, PSA progression was defined as greater than or equal to (\>=) 25 percent (%) and \>=2 nanogram/milliliter (ng/mL) after 12 weeks (in case of no decline in PSA from Baseline), or first PSA increase that is \>=25% and \>=2 ng/mL above the nadir, and which was confirmed by a second value 3 or more weeks later (in case of decline of PSA from Baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response | Week 12 to any time up to 2 years | The PSA response according to Prostate Specific Antigen Working Group 3 criteria was defined as at least 50% decrease in PSA level from Baseline. |
| Overall Survival | Up to 4 years | Overall survival was defined as the time from date of the first dose of abiraterone acetate to the date of death due to any cause. For participants who did not die until the time of analysis, survival time was censored at the time of last contact alive. |
| Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Severity Score | Up to 2 years | The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression was defined as an increase in score of 30% or greater from baseline without decrease in analgesic use. |
| Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Interference Score | Up to 2 years | The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain interference score is mean value for the 7 BPI-SF questions (questions inquiring about the extent of interference with activities by pain) where the extent is ranked from 0 (does not interfere) to 10 (completely interferes). Pain interference progression was defined as an increase in score of 50% or greater from baseline without decrease in analgesic use. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 4 years | An AE is any untoward medical occurrence in a participant who will receive study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly. |
Countries
Brazil
Participant flow
Recruitment details
A total of 46 participants were enrolled into the study and were treated with abiraterone acetate and prednisone. Out of 46 participants, 6 did not fulfill all eligibility criteria and included in the safety population. Thirty-five (35) participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone Acetate Participants received abiraterone acetate 1000 milligram (mg) orally once daily along with prednisone 5 mg orally once daily and androgen deprivation therapy (ADT) as per Investigator's discretion until prostate-specific Antigen (PSA) progression, clinical progression, consent withdrawal, or the occurrence of unacceptable toxicity. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Early study termination | 6 |
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Abiraterone Acetate |
|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 7.71 |
| Race/Ethnicity, Customized Asian/Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Black or African/South American | 7 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 37 Participants |
| Region of Enrollment BRAZIL | 46 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 46 |
| other Total, other adverse events | 45 / 46 |
| serious Total, serious adverse events | 11 / 46 |
Outcome results
Primary
Time to Prostate-specific Antigen (PSA) Progression
Time to PSA progression was calculated from date of enrollment to the date of first documentation of PSA progression. As per Prostate Cancer Clinical Trials Working Group (PCWG2) criteria, PSA progression was defined as greater than or equal to (\>=) 25 percent (%) and \>=2 nanogram/milliliter (ng/mL) after 12 weeks (in case of no decline in PSA from Baseline), or first PSA increase that is \>=25% and \>=2 ng/mL above the nadir, and which was confirmed by a second value 3 or more weeks later (in case of decline of PSA from Baseline).
Time frame: Up to 2 years
Population: The efficacy population included all eligible participants who received at least one dose of any study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate | Time to Prostate-specific Antigen (PSA) Progression | 7.3 Months |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant who will receive study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly.
Time frame: Up to 4 years
Population: The safety population included all participants who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abiraterone Acetate | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 45 Participants |
| Abiraterone Acetate | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 11 Participants |
Secondary
Overall Survival
Overall survival was defined as the time from date of the first dose of abiraterone acetate to the date of death due to any cause. For participants who did not die until the time of analysis, survival time was censored at the time of last contact alive.
Time frame: Up to 4 years
Population: The efficacy population included all eligible participants who received at least one dose of any study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate | Overall Survival | 29.6 Months |
Secondary
Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response
The PSA response according to Prostate Specific Antigen Working Group 3 criteria was defined as at least 50% decrease in PSA level from Baseline.
Time frame: Week 12 to any time up to 2 years
Population: The efficacy population included all eligible participants who received at least one dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone Acetate | Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response | 57.50 Percentage of participants |
Secondary
Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Interference Score
The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain interference score is mean value for the 7 BPI-SF questions (questions inquiring about the extent of interference with activities by pain) where the extent is ranked from 0 (does not interfere) to 10 (completely interferes). Pain interference progression was defined as an increase in score of 50% or greater from baseline without decrease in analgesic use.
Time frame: Up to 2 years
Population: The efficacy population included all eligible participants who received at least one dose of any study drug and with at least 2 BPI-SF assessments after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone Acetate | Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Interference Score | 15.15 Percentage of participants |
Secondary
Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Severity Score
The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression was defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.
Time frame: Up to 2 years
Population: The efficacy population included all eligible participants who received at least one dose of any study drug and with at least 2 BPI-SF assessments after baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone Acetate | Percentage of Participants With Pain Progression as Assessed by Brief Pain Inventory - Short Form (BPI-SF) - Pain Severity Score | 19.44 Percentage of participants |