Metastatic Prostate Cancer
Conditions
Brief summary
This is an open-label, single-arm, multi-center extension study to evaluate safety in patients with mCRPC of YONSA 500 mg (4 x 125 mg qd) with methylprednisolone (4 mg bid). Patients will have successfully completed an 84-day treatment with abiraterone acetate in a previous trial. Results from the final visit of the previous study will be used to determine patient's eligibility for this study. Patients in this study will be eligible to receive open-label YONSA with methylprednisolone for up to 12 months. Pharmacodynamic parameters of serum testosterone and PSA levels will be monitored. Disease progression will be assessed by PCWG2 criteria.
Interventions
DRUGabiraterone acetate with Methylprednisolone
YONSA 500 mg (4 x 125 mg qd) with Methylprednisolone (4 mg bid)
Sponsors
Sun Pharmaceutical Industries Limited
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
* Successful completion of 84 days of treatment with YONSA in Churchill Pharmaceuticals clinical trial, CHL-AA-201 * Last dose of YONSA or Zytiga within 45 days prior to treatment in this study * Written informed consent obtained prior to any study-related procedure being performed * Has in the investigator's opinion, the potential to gain clinical benefit with YONSA treatment * Ongoing therapy with a GnRH agonist or antagonist AND serum testosterone level \<50 ng/dL at screening * Life expectancy of at least 9 months at screening * Subject is willing and able to comply with all protocol requirements assessments * Agrees to protocol-defined use of effective contraception.
Exclusion criteria
* Serious concurrent illness, including psychiatric illness, that would interfere with study participation * Inability to swallow tablets whole * Known hypersensitivity to YONSA, methylprednisolone, or any excipients in study medications * Moderate to severe hepatic impairment (Child-Pugh Classes B and C)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | one year | Adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With Disease Progression | one year | Number of participants who had disease progression |
| Testosterone Levels | Baseline and 360 days | Change in serum testosterone levels from baseline |
| Prostate Specific Antigen Levels | One year | Change in serum testosterone levels after one year of treatment against baseline |
| Testosterone Complete Suppression | 360 days | Proportion of subjects with complete suppression of testosterone levels |
| Percentage of Subjects With Prostate Specific Antigen - 50 Response | 360 days | A decrease of ≥50% reduction from baseline of the study CHL-AA-201 |
Participant flow
Recruitment details
A total of 20 subjects were enrolled in the study. Of these, 9 subjects were previously treated with YONSA and 11 subjects were previously treated with Zytiga in CHL-AA-201. Twelve (60.0%) subjects completed the study
Participants by arm
| Arm | Count |
|---|---|
| Preceding Treatment - Yonsa 84-days treatment | 9 |
| Preceding Treatment - Zytiga 84 day treatment | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 0 |
| Overall Study | Progressive disease | 2 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Preceding Treatment - Yonsa | Preceding Treatment - Zytiga | Total |
|---|---|---|---|
| Age, Customized <75 years | 4 Participants | 5 Participants | 9 Participants |
| Age, Customized ≥75 years | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 11 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 9 | 0 / 11 |
| other Total, other adverse events | 8 / 9 | 9 / 11 |
| serious Total, serious adverse events | 3 / 9 | 1 / 11 |
Outcome results
Primary
Number of Subjects With Adverse Events
Adverse events
Time frame: one year
Population: subjects who were enrolled and who received at least 1 dose of study drug of Yonsa
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preceding Treatment - Yonsa | Number of Subjects With Adverse Events | 8 Participants |
| Preceding Treatment - Zytiga | Number of Subjects With Adverse Events | 9 Participants |
Secondary
Percentage of Subjects With Prostate Specific Antigen - 50 Response
A decrease of ≥50% reduction from baseline of the study CHL-AA-201
Time frame: 360 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preceding Treatment - Yonsa | Percentage of Subjects With Prostate Specific Antigen - 50 Response | 60.0 percentage of number of subjects |
| Preceding Treatment - Zytiga | Percentage of Subjects With Prostate Specific Antigen - 50 Response | 55.6 percentage of number of subjects |
Secondary
Proportion of Subjects With Disease Progression
Number of participants who had disease progression
Time frame: one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Preceding Treatment - Yonsa | Proportion of Subjects With Disease Progression | 1 Participants |
| Preceding Treatment - Zytiga | Proportion of Subjects With Disease Progression | 3 Participants |
p-value: >0.1ANCOVA
Secondary
Prostate Specific Antigen Levels
Change in serum testosterone levels after one year of treatment against baseline
Time frame: One year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preceding Treatment - Yonsa | Prostate Specific Antigen Levels | -60.12 ng/dL | Standard Deviation 115.63 |
| Preceding Treatment - Zytiga | Prostate Specific Antigen Levels | -112.76 ng/dL | Standard Deviation 239.85 |
Secondary
Testosterone Complete Suppression
Proportion of subjects with complete suppression of testosterone levels
Time frame: 360 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preceding Treatment - Yonsa | Testosterone Complete Suppression | 100 percentage of subjects |
| Preceding Treatment - Zytiga | Testosterone Complete Suppression | 87.5 percentage of subjects |
Secondary
Testosterone Levels
Change in serum testosterone levels from baseline
Time frame: Baseline and 360 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preceding Treatment - Yonsa | Testosterone Levels | -6.24 ng/dL | Standard Deviation 2.02 |
| Preceding Treatment - Zytiga | Testosterone Levels | -5.87 ng/dL | Standard Deviation 3.64 |