Prostate Cancer
Conditions
Keywords
Prostate cancer, metastatic, castrate resistant, abiraterone acetate, prednisone, metastatic prostate cancer
Brief summary
The primary goal is to prospectively estimate the median radiographic PFS of African American and Caucasian men with mCRPC to abiraterone acetate and prednisone.
Detailed description
This is a non-comparative pilot open-label, parallel arm, multicenter study of abiraterone acetate in African American and Caucasian men with mCRPC. Patients will self-report on race and 50 patients will be enrolled into each group. Patients will be treated on open-label treatment until evidence of disease progression as defined by Prostate Cancer Working Group Two (PCWG2) definition or until two years at which point they will roll over to the standard of care at that time. The study agent abiraterone acetate will be administered by the patient at a dose of 1000mg orally once daily with prednisone 5 mg BID in 4-week cycles throughout the treatment period.
Interventions
DRUGAbiraterone acetate
DRUGPrednisone
Sponsors
Duke University
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
* Male, age ≥ 18 years * Karnofsky performance status ≥ 70 * Life expectancy of ≥ 12 months * 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, and should be able to swallow tablets whole, without crushing/chewing tablets * 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 and sponsor during the study and for 1 week after last dose of abiraterone acetate * Adequate laboratory parameters * Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are excluded * Radiographic evidence of metastatic disease; evaluable non-target lesions and/or bone only metastasis are permitted * Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed. Screening serum testosterone must be \<50 ng/dl * PSA ≥ 2.0 ng/mL * Evidence of of castration resistant disease on ADT as evidenced by one of the following: * Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR * 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR * CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to modified PCWG2 criteria or modified RECIST 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies) * A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide) * A minimum of 4 weeks elapsed off of sipuleucel-T prior to start of study drug * A minimum of 4 weeks from any major surgery prior to start of study drug * Self-reported race of either African American or Caucasian * Ability to swallow, retain, and absorb oral medication
Exclusion criteria
* Prior treatment with abiraterone acetate or enzalutamide * Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated * Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid * Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients * Pathological finding consistent with small cell carcinoma of the prostate * Symptomatic Liver or visceral organ metastasis * Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents * Known brain metastasis * Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC * Previously treated with ketoconazole for prostate cancer for greater than 7 days * Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1 * 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. * Poorly controlled diabetes * 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 II-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline * Atrial Fibrillation or other cardiac arrhythmia requiring therapy * Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months * Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1 * Any condition which, in the opinion of the investigator, would preclude participation in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Radiographic Progression Free Survival (PFS) | up to 2 years | Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Working Group 2 criteria, or to death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median rPFS was estimated using a Kaplan-Meier curve. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PSA Response | Baseline and up to 2 years | Percent of men with Prostate Specific Antigen (PSA) declines \> 30%, \> 50% and \> 90% |
| Median Time to PSA Progression | up to 2 years | Time to PSA progression as defined by PCWG 2 criteria is the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later. |
| Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml | up to 2 years | Number of men who achieve a PSA decline to \< 0.1 and \< 0.2 ng/ml |
| Percent of Subjects Experiencing Hypertension | up to 2 years | Incidence and grade of hypertension in the two populations. (Grade 1: Systolic BP 120 to 139 mmHg or diastolic BP 80 to 89 mmHg, Grade 2: Systolic BP 140 to 159 mmHg or diastolic BP 90 to 99 mmHg, Grade 3: Systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg, Grade 4: Life-threatening consequences, urgent intervention indicated) |
| Overall Survival | up to 3 years | Length of patient's life after starting study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| White Patients self identifying as white who received the study regimen | 50 |
| Black Patients self identifying as black who received the study regimen | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Black | Total | White |
|---|---|---|---|
| Age, Continuous | 69.05 years STANDARD_DEVIATION 9.2 | 68.5 years STANDARD_DEVIATION 8.5 | 68.2 years STANDARD_DEVIATION 7.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants | 50 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 50 Participants | 50 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 50 Participants | 100 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 50 / 50 | 50 / 50 |
| serious Total, serious adverse events | 14 / 50 | 14 / 50 |
Outcome results
Primary
Median Radiographic Progression Free Survival (PFS)
Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Working Group 2 criteria, or to death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median rPFS was estimated using a Kaplan-Meier curve.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate and Prednisone: White Men | Median Radiographic Progression Free Survival (PFS) | 16.8 months |
| Abiraterone Acetate and Prednisone: African American Men | Median Radiographic Progression Free Survival (PFS) | 16.6 months |
Secondary
Change in PSA Response
Percent of men with Prostate Specific Antigen (PSA) declines \> 30%, \> 50% and \> 90%
Time frame: Baseline and up to 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abiraterone Acetate and Prednisone: White Men | Change in PSA Response | Percent of men with PSA declines > 30% | 78 percentage of participants |
| Abiraterone Acetate and Prednisone: White Men | Change in PSA Response | Percent of men with PSA declines > 50% | 66 percentage of participants |
| Abiraterone Acetate and Prednisone: White Men | Change in PSA Response | Percent of men with PSA declines > 90% | 38 percentage of participants |
| Abiraterone Acetate and Prednisone: African American Men | Change in PSA Response | Percent of men with PSA declines > 30% | 82 percentage of participants |
| Abiraterone Acetate and Prednisone: African American Men | Change in PSA Response | Percent of men with PSA declines > 50% | 74 percentage of participants |
| Abiraterone Acetate and Prednisone: African American Men | Change in PSA Response | Percent of men with PSA declines > 90% | 48 percentage of participants |
Secondary
Median Time to PSA Progression
Time to PSA progression as defined by PCWG 2 criteria is the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate and Prednisone: White Men | Median Time to PSA Progression | 11.5 months |
| Abiraterone Acetate and Prednisone: African American Men | Median Time to PSA Progression | 16.6 months |
Secondary
Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml
Number of men who achieve a PSA decline to \< 0.1 and \< 0.2 ng/ml
Time frame: up to 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abiraterone Acetate and Prednisone: White Men | Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml | PSA decline to < 0.1 | 4 Participants |
| Abiraterone Acetate and Prednisone: White Men | Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml | PSA decline to < 0.2 | 5 Participants |
| Abiraterone Acetate and Prednisone: African American Men | Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml | PSA decline to < 0.1 | 9 Participants |
| Abiraterone Acetate and Prednisone: African American Men | Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml | PSA decline to < 0.2 | 13 Participants |
Secondary
Overall Survival
Length of patient's life after starting study
Time frame: up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate and Prednisone: White Men | Overall Survival | 35.7 months |
| Abiraterone Acetate and Prednisone: African American Men | Overall Survival | 35.9 months |
Secondary
Percent of Subjects Experiencing Hypertension
Incidence and grade of hypertension in the two populations. (Grade 1: Systolic BP 120 to 139 mmHg or diastolic BP 80 to 89 mmHg, Grade 2: Systolic BP 140 to 159 mmHg or diastolic BP 90 to 99 mmHg, Grade 3: Systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg, Grade 4: Life-threatening consequences, urgent intervention indicated)
Time frame: up to 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abiraterone Acetate and Prednisone: White Men | Percent of Subjects Experiencing Hypertension | All grades | 20 Participants |
| Abiraterone Acetate and Prednisone: White Men | Percent of Subjects Experiencing Hypertension | Grades 3 and 4 | 8 Participants |
| Abiraterone Acetate and Prednisone: African American Men | Percent of Subjects Experiencing Hypertension | All grades | 23 Participants |
| Abiraterone Acetate and Prednisone: African American Men | Percent of Subjects Experiencing Hypertension | Grades 3 and 4 | 12 Participants |