Prostate Cancer
Conditions
Keywords
African American men, metastatic prostate cancer, castration resistant
Brief summary
This is a pilot study of abiraterone acetate in African American/Black patients with castration-resistant prostate cancer. The primary objective is to determine the correlation between germline polymorphisms and antitumor activity (as defined by a decline in PSA of ≥ 30%) in African American patients with castration-resistant prostate cancer treated with abiraterone acetate. Patients will receive abiraterone acetate until the time of disease progression, in the absence of prohibitive toxicities. Patients will be followed for disease progression and survival.
Interventions
DRUGAbiraterone Acetate
Abiraterone acetate 1000 mg orally daily (supplied as four 250 mg tablets) and prednisone 5 mg orally twice daily
Sponsors
Icahn School of Medicine at Mount Sinai
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
* 1\. Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study * Be willing/able to adhere to the prohibitions and restrictions specified in this protocol * Written Authorization for Use and Release of Health and Research Study Information * African American or Black (by self identification) * Male aged 18 years and above * Histologically or cytologically confirmed adenocarcinoma of the prostate * Metastatic disease documented by standard imaging * Progressive prostate cancer based on either rising PSA, new bone metastases, or progression of measurable disease according to PCWG2 12 guidelines. * Patients in either of the following clinical states will be eligible for enrollment: i. No prior chemotherapy; ii. Patients previously treated with 1-2 prior chemotherapy regimens permitted, one of which must have been included docetaxel * Surgically or medically castrated, with testosterone levels of \< 50 ng/dl. * Patients previously treated with an anti-androgen must demonstrate progression off of the anti-androgen. * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 * Have a baseline serum potassium of ≥ 3.5 mEq/L * Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels \< 1.5 x ULN * Have a serum albumin of ≥ 3.0 g/dL * Total bilirubin ≤ 1.5 x ULN * Have a platelet count of ≥ 100,000/μL * Have an absolute neutrophil count of \> 1500 cell/mm3 * Have a calculated creatinine clearance ≥ 60 mL/min * Have a hemoglobin of ≥ 9.0 g/dL * Able to swallow the study drug as a whole tablet * Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken * Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the study and for 1 week after last dose of abiraterone acetate
Exclusion criteria
* Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated * Known brain metastasis * Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg) Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment * Active or symptomatic viral hepatitis or chronic liver disease * History of pituitary or adrenal dysfunction * Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline * Administration of an investigational therapeutic within 30 days of screening * Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements * Have poorly controlled diabetes * Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents * Have a pre-existing condition that warrants long-term corticosteroid use in excess of study dose * Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ≥ 30% Change in PSA | baseline and 12 weeks | The primary objective of this study is to determine a correlation between inherited genetic polymorphisms and antitumor activity (as defined by a decline in PSA of ≥ 30%) in AA patients with castration-resistant prostate cancer treated with Abiraterone. The primary endpoint is the percent change in PSA from baseline to 12 weeks. A decline of ≥ 30% will be correlated with germline SNPs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Assessment | up to 12 weeks | Post-treatment changes in measurable disease by RECIST - Response Evaluation Criteria in Solid Tumors Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions |
| Time to Progression | up to 12 weeks | post-treatment changes in measurable disease by time to disease progression (as per PCWG2 guidelines) |
| Bone Scan | up to 12 weeks | post-treatment changes in bone scans (as per PCWG2 guidelines) (no new lesions versus new lesions.) |
| Safety of Abiraterone | up to 12 weeks | To determine the safety of abiraterone Adverse events as defined by CTCAE v4. Number of participants with serious adverse events grade 4 or 5 |
| Testosterone | up to 12 weeks | Post-treatment changes in testosterone |
Countries
United States
Participant flow
Recruitment details
Recruitment began in Dec 2012, with enrollment from April 2014 to March 2016.
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone Acetate Abiraterone Acetate: Abiraterone acetate 1000 mg orally daily (supplied as four 250 mg tablets) and prednisone 5 mg orally twice daily | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | not evaluable | 1 |
Baseline characteristics
| Characteristic | Abiraterone Acetate |
|---|---|
| Age, Continuous | 66 years |
| Number of prior systemic therapies | 3 prior therapies |
| Performance Status: ECOG ECOG 0 | 8 Participants |
| Performance Status: ECOG ECOG 1 | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Number of Participants With ≥ 30% Change in PSA
The primary objective of this study is to determine a correlation between inherited genetic polymorphisms and antitumor activity (as defined by a decline in PSA of ≥ 30%) in AA patients with castration-resistant prostate cancer treated with Abiraterone. The primary endpoint is the percent change in PSA from baseline to 12 weeks. A decline of ≥ 30% will be correlated with germline SNPs.
Time frame: baseline and 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone Acetate | Number of Participants With ≥ 30% Change in PSA | 9 Participants |
Secondary
Bone Scan
post-treatment changes in bone scans (as per PCWG2 guidelines) (no new lesions versus new lesions.)
Time frame: up to 12 weeks
Population: data not collected
Secondary
Response Assessment
Post-treatment changes in measurable disease by RECIST - Response Evaluation Criteria in Solid Tumors Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time frame: up to 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abiraterone Acetate | Response Assessment | PR | 9 Participants |
| Abiraterone Acetate | Response Assessment | SD | 1 Participants |
Secondary
Safety of Abiraterone
To determine the safety of abiraterone Adverse events as defined by CTCAE v4. Number of participants with serious adverse events grade 4 or 5
Time frame: up to 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone Acetate | Safety of Abiraterone | 0 Participants |
Secondary
Testosterone
Post-treatment changes in testosterone
Time frame: up to 12 weeks
Population: data not collected
Secondary
Time to Progression
post-treatment changes in measurable disease by time to disease progression (as per PCWG2 guidelines)
Time frame: up to 12 weeks
Population: data not collected