Castration-resistant Prostate Cancer, Stage IV Prostate Cancer
Conditions
Brief summary
This randomized phase II trial studies the best way to give abiraterone acetate in treating patients with castration-resistant prostate cancer. Abiraterone acetate is effective in treating castrate resistant prostate cancer and is taken in the fasting state. However, the body's absorption of abiraterone is increased with food intake. This study will test the whether a lower dose of abiraterone taken with food has a similar effect on prostate specific antigen (PSA) compared to full dose taken fasting.
Detailed description
PRIMARY OBJECTIVES: I. To compare the pharmacodynamic effect of reduced dose (250mg daily) abiraterone acetate in the prandial state (250mg-Fed) to the full, standard 1000mg daily dose in the fasting state (1000mg-Fasting) as assessed by change in serum prostate-specific antigen (PSA). SECONDARY OBJECTIVES: I. To evaluate the effect of prandial states on plasma levels and the intra-patient pharmacokinetic variability of abiraterone acetate. II. To evaluate the safety profile of reduced dose abiraterone acetate taken in the prandial state. III. To evaluate the pharmacodynamic effect of reduced dose abiraterone acetate in the prandial state as assessed by reduction in the extra-gonadal androgen dihydroepiadrosterone sulfate (DHEA-S) and dihydroepiandrostenedione (DHEA). IV. To evaluate the effect of prandial state on time to disease progression (Working group criteria). OUTLINE: Patients are randomized to one of two treatment arms. ARM I: Patients receive abiraterone acetate orally (PO) daily first thing in morning after an overnight fast of at least 8 hours. ARM II: Patients receive abiraterone acetate PO daily within 30 minutes of a conventional low-fat breakfast. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Both arms will also be treated with prednisone 5mg twice daily. After completion of study treatment, patients are followed up within 30 days.
Interventions
DRUGabiraterone acetate
Given PO
Sponsors
National Cancer Institute (NCI)
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed prostate cancer with progressive disease defined as either: * 2 or more new lesions on bone scan or * Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria or * Rising prostate-specific antigen (PSA): PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart * Evidence of castration resistance defined as disease progression despite a testosterone level \< 50 ng/dL (or surgical castration) * Any prior therapy for castrate disease is acceptable except prior abiraterone, which is excluded; a minimum washout of 28 days for any other anticancer therapy prior to first dose of study drug is required * Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug * Denosumab or zoledronic acid are allowed * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Total bilirubin =\< 1.5 x the upper limit of normal * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid (other than prednisone =\< 10 mg/day) within 4 weeks prior to first dose of study drug * Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug is excluded with the following exceptions: * Conventional multivitamin supplements * Selenium * Lycopene * Soy supplements * Inability to swallow capsules or known gastrointestinal malabsorption * History of other malignancies, with the exception of adequately treated non-melanoma skin cancer or adequately treated superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for \>= 5 years from enrollment * Blood pressure that is not controlled despite \> 2 oral agents (systolic blood pressure \[SBP\] \> 160 and diastolic blood pressure \[DBP\] \> 90 documented during the screening period with no subsequent blood pressure readings \< 160/100) * Serum potassium (K)+ \< 3.5 mmoL/L on more than one reading within the screening period * Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled * Active psychiatric illness/social situations that would limit compliance with protocol requirements * New York Heart Association (NYHA) class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure) * Concurrent therapy with strong inhibitors or inducers of Cytochrome P450 (CYP)3A4 due to concerning possible drug-drug interactions with abiraterone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PSA Level | From baseline to 12 weeks | Data were analyzed on a log scale: log(week 12) - log(baseline) = log ratio. Smaller (more negative) values indicate a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Assessed up to 3 years | Time to PSA progression (25% increase from baseline), radiographic progression, or death. |
| Adrenal Androgen Production (DHEA-S) | Cycle 4 (4 months) | Extragonadal serum adrogen |
| Number of Participants With Adverse Events (AEs) | Assessed up to 1 year | Patients with grade 3 or higher AE (CTCAE Version 4.03) |
| Peak Plasma Concentration of Abiraterone | Up to 4 months | Analyzed on a log scale due to skewness of distribution |
Countries
Singapore, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Fasting) Patients receive abiraterone acetate PO daily first thing in morning after an overnight fast of at least 8 hours.
abiraterone acetate: Given PO | 36 |
| Arm II (Fed) Patients receive abiraterone acetate PO daily within 30 minutes of a conventional low-fat breakfast.
abiraterone acetate: Given PO | 36 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Arm I (Fasting) | Arm II (Fed) | Total |
|---|---|---|---|
| Age, Continuous | 74 years | 72 years | 73 years |
| Race/Ethnicity, Customized African American | 5 Participants | 11 Participants | 16 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 17 Participants | 43 Participants |
| Region of Enrollment Singapore | 4 participants | 6 participants | 10 participants |
| Region of Enrollment United States | 32 participants | 30 participants | 62 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 34 | 4 / 34 |
| other Total, other adverse events | 32 / 34 | 32 / 34 |
| serious Total, serious adverse events | 5 / 34 | 2 / 34 |
Outcome results
Primary
Change in PSA Level
Data were analyzed on a log scale: log(week 12) - log(baseline) = log ratio. Smaller (more negative) values indicate a better outcome.
Time frame: From baseline to 12 weeks
Population: Two patients in each arm had missing data at 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Fasting) | Change in PSA Level | -1.19 log ratio | Standard Error 0.29 |
| Arm II (Fed) | Change in PSA Level | -1.59 log ratio | Standard Error 0.27 |
p-value: <0.1t-test, 1 sided
Secondary
Adrenal Androgen Production (DHEA-S)
Extragonadal serum adrogen
Time frame: Cycle 4 (4 months)
Population: 29 patients had missing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Fasting) | Adrenal Androgen Production (DHEA-S) | 13.30 microgram per deciliter | Standard Error 1.47 |
| Arm II (Fed) | Adrenal Androgen Production (DHEA-S) | 10.22 microgram per deciliter | Standard Error 1.33 |
p-value: 0.13t-test, 2 sided
Secondary
Number of Participants With Adverse Events (AEs)
Patients with grade 3 or higher AE (CTCAE Version 4.03)
Time frame: Assessed up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Fasting) | Number of Participants With Adverse Events (AEs) | 6 Participants |
| Arm II (Fed) | Number of Participants With Adverse Events (AEs) | 11 Participants |
p-value: 0.26Fisher Exact
Secondary
Peak Plasma Concentration of Abiraterone
Analyzed on a log scale due to skewness of distribution
Time frame: Up to 4 months
Population: Three patients had missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Fasting) | Peak Plasma Concentration of Abiraterone | 5.39 log(ng/mL) | Standard Error 0.19 |
| Arm II (Fed) | Peak Plasma Concentration of Abiraterone | 4.65 log(ng/mL) | Standard Error 0.21 |
p-value: 0.012t-test, 2 sided
Secondary
Progression-free Survival (PFS)
Time to PSA progression (25% increase from baseline), radiographic progression, or death.
Time frame: Assessed up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Fasting) | Progression-free Survival (PFS) | 8.6 Months |
| Arm II (Fed) | Progression-free Survival (PFS) | 8.6 Months |
p-value: 0.38Log Rank