Prostate Cancer, Prostatic Neoplasm
Conditions
Keywords
abiraterone acetate, prednisone, zytiga
Brief summary
The purpose of this study is to show that abiraterone acetate plus prednisone added to the current standard of care, gonadotropin-releasing hormone (GnRH) decreases prostate specific antigen (PSA) and prolongs the time until it is evident that the cancer has grown. Additionally, safety information about abiraterone acetate in combination with prednisone will be collected. This will include looking at what side effects occur, how often they occur, and for how long they last.
Detailed description
This is a Phase 2, prospective, multicenter, open-label, single-arm study of abiraterone acetate plus prednisone in men with non-metastatic, castration-resistant prostate cancer (CRPC) who have a rising PSA despite castrate levels of testosterone. The study consists of Screening Phase (up to 4 weeks), Core Study Treatment Phase (comprised of six 28-day cycles), a Pre-metastatic Disease Follow-up Phase, an Optional Drug Holiday Phase; and a 30-day Safety Follow-up Visit. Each treatment cycle will last 28 days. Participating participants will receive study agents (Abiraterone acetate 1000 mg/day plus prednisone 5 mg/day, orally) continually during the study. If the partcipants elects to participate in the Optional Drug Holiday Phase, participants will discontinue abiraterone acetate plus prednisone and ADT. Participants will have the option to return to study medication during the first year of the Optional Drug Holiday Phase if there is evidence of rising PSA but no metastasis based on study imaging. If participants do no elect to participate, they will continue with the core study treatment as per protocol. The study will end when all participated participants have disease progression or end of the 2-year period (if participants participated in the Optional Drug Holiday Phase). Participants will be required to return to the study site 30 days after receiving the last dose of abiraterone acetate for safety follow-up.
Interventions
DRUGabiraterone acetate in combination with prednisone
Abiraterone acetate will be taken as 4 x 250 mg tablets by mouth (PO) once daily. Prednisone will be taken as 2 x 2.5 mg tablets PO once daily.
Sponsors
Janssen Biotech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * Be a male \>= 18 years of age * Have adenocarcinoma of the prostate * Currently receiving continuous treatment with Gonadotropin-releasing hormone (GnRH) monotherapy for at least 6 months before or have undergone surgical removal of the testicles * Serum testosterone of \< 50 ng/dL(\< 2.0 nM) * Have rising PSA defined as a PSA of \>= 10 ng/mL obtained at screening or PSADT of ≤ 10 months with the first of the 3 consecutive PSA values used to calculate PSADT ≥ 2.0 ng/mL * Have an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 * Be capable of swallowing study agents whole as a tablet * Be willing/able to adhere to the prohibitions and restrictions specified in this protocol Major
Exclusion criteria
* Have prior or current evidence of local disease progression or metastatic disease as defined by modified response evaluation criteria in solid tumors (RECIST) criteria * Have received chemotherapy for treatment of castrate-resistant prostate cancer; however, if a patient received chemotherapy in an adjuvant setting, prior to having CRPC, for castrate-sensitive prostate cancer, the patient is still eligible * Are currently receiving any antiandrogen therapy (eg, bicalutamide, flutamide, or nilutamide). * If previously treated with antiandrogen therapy, there must be documentation of at least 2 consecutive rising PSA values at least 2 weeks apart obtained prior to screening * If previously treated with flutamide, at least 1 of the PSA values must be obtained 4 weeks or more after flutamide discontinuation. * If previously treated with bicalutamide or nilutamide, at least 1 of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation * Have previously received agents having any CYP17 inhibitory activity for the treatment of prostate cancer, such as ketoconazole * Have previously received aminoglutethimide * Have an active infection or other medical condition that would contraindicate prednisone use * Have uncontrolled hypertension * Have active hepatitis or chronic liver disease * Have clinically significant heart disease * Have poorly controlled diabetes * Have received an investigational therapeutic within 30 days of screening * Have partners of childbearing potential and are not willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate. * Individuals with a history of a non-prostate malignancy are ineligible for this study with the following exceptions. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: basal cell or squamous cell carcinoma of the skin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) During the Core Study | End of core study visit (Approximately at Month 6) | Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Radiographic Evidence of Disease Progression (TTRP) | Maximum up to Month 30.5 | Time to radiographic evidence of disease progression is defined as the time interval from the date of enrollment (Day 1) to the date of disease progression. A participant was considered as progressed by bone scan if: 1) The appearance of greater than or equal to (\>=) 2 new lesions, and, following the first assessment, a confirmatory scan performed 6 or more weeks later that shows a minimum of 2 or more additional new lesions, 2) If \>=2 new lesions are seen on scans following the first assessment, the confirmation is still required after 6 weeks; however, 2 addition lesions are not required to confirm progression, and 3) The date of progression is the date of the first scan that shows the changes. |
| Time to Prostate-Specific Antigen (PSA) Progression | Maximum up to Month 30.5 | Time to PSA progression is defined as the time interval from the date of enrollment (Day 1) to the date of first evidence of PSA progression. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase and an absolute increase of 2 nanogram (ng)/milliliter (mL) or more, which is confirmed by a second value obtained in 3 or more weeks. |
| Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) Levels After 3 Cycles of Treatment | End of Cycle 3 (Approximately Month 3) | Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed. Decrease in PSA levels represented improvement. |
Countries
United States
Contacts
STUDY_DIRECTORJanssen Services, LLC. Clinical Trial
Janssen Biotech, Inc.
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone Acetate Plus Prednisone Participants were given abiraterone acetate 1000 milligrams (mg) (4\*250 mg) tablets plus prednisone 5 mg (2\*2.5 mg) tablets orally once daily in core study treatment phase (comprised of 6, 28-day cycles). After the core study treatment phase, participants who entered the pre-metastatic disease follow-up phase continued the study treatment until radiographic confirmation of disease progression, intolerable toxicity, investigator's decision, and withdrawal by participant or until the sponsor decided to stop the trial. As per amendment 6, participants who opted for the drug holiday phase stopped abiraterone acetate plus prednisone, and androgen-deprivation therapy (ADT), with the option to restart treatment within the first year if prostate-specific antigen (PSA) levels increased without metastasis. Those who did not opt for the drug holiday phase continued treatment. The study ended when all participants had disease progression or completed the 2-year period (for drug holiday participants) (up to 140 months; 153 Cycles). Post-metastatic disease follow-up phase was also discontinued, though participants already enrolled at the time of protocol amendment 6 remained on study. A safety follow-up visit was required 30 days after the last dose of abiraterone acetate. | 131 |
| Total | 131 |
Baseline characteristics
| Characteristic | Abiraterone Acetate Plus Prednisone |
|---|---|
| Age, Continuous | 71.2 Years STANDARD_DEVIATION 8.82 |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 122 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 108 Participants |
| Region of Enrollment United States | 131 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 131 |
| other Total, other adverse events | 120 / 131 |
| serious Total, serious adverse events | 61 / 131 |
Outcome results
Primary
Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) During the Core Study
Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed.
Time frame: End of core study visit (Approximately at Month 6)
Population: Efficacy evaluable set included all participants who received at least one dose of study drug, completed at least 1 cycle of treatment and had at least 1 post-baseline PSA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone Acetate Plus Prednisone | Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) During the Core Study | 86.9 Percentage of participants |
Secondary
Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) Levels After 3 Cycles of Treatment
Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed. Decrease in PSA levels represented improvement.
Time frame: End of Cycle 3 (Approximately Month 3)
Population: Efficacy evaluable set included all participants who received at least 1 dose of study drug, completed at least 1 cycle of treatment and had at least 1 post-baseline PSA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone Acetate Plus Prednisone | Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) Levels After 3 Cycles of Treatment | 85.2 Percentage of Participants |
Secondary
Time to Prostate-Specific Antigen (PSA) Progression
Time to PSA progression is defined as the time interval from the date of enrollment (Day 1) to the date of first evidence of PSA progression. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase and an absolute increase of 2 nanogram (ng)/milliliter (mL) or more, which is confirmed by a second value obtained in 3 or more weeks.
Time frame: Maximum up to Month 30.5
Population: All enrolled set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate Plus Prednisone | Time to Prostate-Specific Antigen (PSA) Progression | 28.7 Months |
Secondary
Time to Radiographic Evidence of Disease Progression (TTRP)
Time to radiographic evidence of disease progression is defined as the time interval from the date of enrollment (Day 1) to the date of disease progression. A participant was considered as progressed by bone scan if: 1) The appearance of greater than or equal to (\>=) 2 new lesions, and, following the first assessment, a confirmatory scan performed 6 or more weeks later that shows a minimum of 2 or more additional new lesions, 2) If \>=2 new lesions are seen on scans following the first assessment, the confirmation is still required after 6 weeks; however, 2 addition lesions are not required to confirm progression, and 3) The date of progression is the date of the first scan that shows the changes.
Time frame: Maximum up to Month 30.5
Population: All enrolled set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate Plus Prednisone | Time to Radiographic Evidence of Disease Progression (TTRP) | 41.4 Months |