Prostate Cancer
Conditions
Brief summary
The addition of abiraterone acetate to standard treatment of radiotherapy and short-term androgen deprivation will increase the frequency of undetectable PSA.
Detailed description
This is a single arm two-site study of 37 men with unfavorable prostate cancer (defined as having a single high risk factor). Patients will concurrently initiate 6 months of standard-of-care GNRH agonist therapy and once daily abiraterone acetate/prednisone. After 2 months of lead-in hormonal treatment, definitive standard-of-care prostate/seminal vesicle radiotherapy will be delivered, to a total dose of 75-80 Gy.
Interventions
DRUGAbiraterone acetate
1000 mg orally once a day for 6 months.
LHRH analog (at discretion of treating physician) will be administered over 6 months (for example, leuprolide acetate 22.5mg IM or goserelin acetate 10.8mg SC given every 3 months for 2 doses).
RADIATIONRadiation Therapy
Daily (Monday-Friday) for 8 weeks, final dose of 75-80 Gy
DRUGPrednisone
5 mg tablet once daily for 6 months.
Sponsors
Janssen Pharmaceuticals
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
* One of the following high risk criteria: * Gleason Score 7 with PSA ≤ 20 ng/ml and clinical T1-2, or * Gleason Score 8-10, PSA ≤ 20 ng/ml and clinical T1-2a, or * PSA 10.1-40 ng/ml with GS \< 7 and clinical T1-2, or * Clinical T3 with Gleason Score \< 7 and PSA ≤ 10 ng/ml. * ECOG Performance Status ≤ 1 * Digital rectal exam within 90 days of registration on study * CBC with differential with adequate bone marrow function defined as follows: * Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets \> 100,000/µL and Hemoglobin ≥ 9g/dL * Serum potassium ≥ 3.5 mEq/L * Serum albumin \> 3.0 g/dl * Total bilirubin \< 1.5 X of institutional upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) \< 1.5 X ULN * Calculated creatinine clearance \> 60 mL/min * Age \> 18 years * Able to swallow a whole tablet and take abiraterone acetate on an empty stomach (defined as no food for two hours before and one hour after abiraterone acetate ingestion) * Ability to understand and sign a written informed consent document * Written authorization for use and release of health and research study information has been obtained * Be willing/able to adhere to the prohibitions and restrictions specified in this protocol * Subjects who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protections as determined acceptable by the principal investigator during the study and for 1 week after the last dose of abiraterone acetate.
Exclusion criteria
* Bone, visceral or soft tissue metastasis, including lymph nodes (\>2 cm in longest diameter) * Prior therapy for prostate cancer \[Exceptions: LHRH agonist or antagonist may have been initiated within 30 days prior to enrollment. Bicalutamide may have been given within 60 days of enrollment as long as it has been stopped at least 7 days before enrollment and total duration was no longer than 30 days. This is to allow enrollment of those who have been given bicalutamide as a bridge for LHRH agonist/antagonist. It is highly unlikely a short non-overlapping course of bicalutamide will interact with abiraterone acetate in a measurable way. Previous alpha-reductase inhibitor use allowed IF patient has not been taking for at least 30 days prior to abiraterone acetate initiation, OR if alpha reductase inhibitor was not used as a primary treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within eligibility when doubled. \] * Known serum testosterone ≤ 150 ng/dl or symptoms of hypogonadism (fatigue, hot flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior to ADT initiation not explained by other medical co-morbidity OR history of testosterone supplement. If questionable, serum testosterone level greater than 150 ng/dl can be used to exclude hypogonadism. * Previous malignancy within 3 years other than non-melanomatous skin cancer and non-muscle invasive bladder cancer * Previous pelvic radiotherapy that would prevent prostate/SV irradiation * 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 therapy * History of gastrointestinal disorders that may interfere with the absorption of study drug (including gastric bypass surgery) * Concurrent spironolactone use * Significant concurrent medical condition that would make prednisone/prednisolone use contraindicated or would interfere with the patient's ability to participate in the trial * Receiving any investigational agents currently or within 30 days prior to study screening * Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate, prednisone or their excipients * Active co-morbidity, defined as follows: * Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or C * History of pituitary or adrenal dysfunction * Poorly controlled diabetes mellitus (A1c \>9% or history of complications including peripheral neuropathy, end organ damage, hospitalization, amputation) * Poorly controlled glaucoma * 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 known cardiac ejection fraction measurement of \< 50% at baseline. * Clinical evidence of active infection of any type, including active or symptomatic viral hepatitis. * Known immune deficiency and/or HIV-positive patients * Any medical condition that warrants long-term corticosteroid use in excess of study dose * Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) * Any condition that in the opinion of the Principal Investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing the study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Undetectable PSA (Prostate-Specific Antigen) at 1 Year | 1 year | The percentage of patients with undetectable PSA after 1 year will be calculated. Undetectable PSA is defined as a measurement of \<0.1 ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Nadir Value | 1 year, 2 years | The lowest PSA value from the start of study therapy. |
| Percentage of Participants With Biochemical Progression-free Survival (BPFS) | 36 and 48 months | Disease progression defined as Phoenix RTOG definition of nadir PSA + 2ng/ml or initiation of salvage therapy not imaging. The two outcomes use different measures (biochemical as measured by PSA increase vs radiographic as measured by imaging), yielding different results in this case. |
| Metastasis or Systemic Therapy | up to 5 years (60 months) | Time to either imaging indicating metastasis or beginning a new systemic therapy. This is a distinctly different measure from number 4 above. The two outcomes use different measures (biochemical as measured by PSA increase vs radiographic as measured by imaging), yielding different results in this case. |
| Time to PSA Nadir | 1 year | The median time in months to the lowest PSA value from the start of study therapy. |
| PSA < 1.5ng/ml in Setting of Non-castrate Testosterone | 1 year, 2 years, 3 years, 4 years, 5 years | Percentage of men with 1, 2, 3, 4 and 5 year PSA \< 1.5ng/ml in setting of non-castrate testosterone. |
| Safety and Tolerability | 6 months | The number of patients experiencing an adverse event of at least grade 3 that is possibly, probably, or definitely related to study therapy per CTCAE version 4.0. |
| Testosterone Recovery | up to 5 years | Time to testosterone recovery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone+Radiotherapy+ADT Abiraterone Acetate, Radiotherapy and Short Term Androgen Deprivation. Prednisone will be prescribed concurrently with Abiraterone acetate. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Abiraterone+Radiotherapy+ADT |
|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 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 | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 37 |
| other Total, other adverse events | 36 / 37 |
| serious Total, serious adverse events | 4 / 37 |
Outcome results
Primary
Percentage of Patients With Undetectable PSA (Prostate-Specific Antigen) at 1 Year
The percentage of patients with undetectable PSA after 1 year will be calculated. Undetectable PSA is defined as a measurement of \<0.1 ng/mL.
Time frame: 1 year
Population: This analysis includes all patients that completed protocol therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone+Radiotherapy+ADT | Percentage of Patients With Undetectable PSA (Prostate-Specific Antigen) at 1 Year | 54.54 percentage of participants |
Secondary
Metastasis or Systemic Therapy
Time to either imaging indicating metastasis or beginning a new systemic therapy. This is a distinctly different measure from number 4 above. The two outcomes use different measures (biochemical as measured by PSA increase vs radiographic as measured by imaging), yielding different results in this case.
Time frame: up to 5 years (60 months)
Population: Men with unfavorable prostate cancer (defined ad having a single high risk factor)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Abiraterone+Radiotherapy+ADT | Metastasis or Systemic Therapy | 60 months |
Secondary
Percentage of Participants With Biochemical Progression-free Survival (BPFS)
Disease progression defined as Phoenix RTOG definition of nadir PSA + 2ng/ml or initiation of salvage therapy not imaging. The two outcomes use different measures (biochemical as measured by PSA increase vs radiographic as measured by imaging), yielding different results in this case.
Time frame: 36 and 48 months
Population: Men with unfavorable prostate cancer (defined as having a single high risk factor)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abiraterone+Radiotherapy+ADT | Percentage of Participants With Biochemical Progression-free Survival (BPFS) | 48 months | 96.96 percentage of participants |
| Abiraterone+Radiotherapy+ADT | Percentage of Participants With Biochemical Progression-free Survival (BPFS) | 36 months | 96.96 percentage of participants |
Secondary
PSA < 1.5ng/ml in Setting of Non-castrate Testosterone
Percentage of men with 1, 2, 3, 4 and 5 year PSA \< 1.5ng/ml in setting of non-castrate testosterone.
Time frame: 1 year, 2 years, 3 years, 4 years, 5 years
Population: Men with unfavorable prostate cancer (defined as having a single high risk factor)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abiraterone+Radiotherapy+ADT | PSA < 1.5ng/ml in Setting of Non-castrate Testosterone | 1 year | 100 percentage of patients |
| Abiraterone+Radiotherapy+ADT | PSA < 1.5ng/ml in Setting of Non-castrate Testosterone | 2 years | 100 percentage of patients |
| Abiraterone+Radiotherapy+ADT | PSA < 1.5ng/ml in Setting of Non-castrate Testosterone | 3 years | 90.91 percentage of patients |
| Abiraterone+Radiotherapy+ADT | PSA < 1.5ng/ml in Setting of Non-castrate Testosterone | 4 years | 90.91 percentage of patients |
| Abiraterone+Radiotherapy+ADT | PSA < 1.5ng/ml in Setting of Non-castrate Testosterone | 5 years | 90.91 percentage of patients |
Secondary
PSA Nadir Value
The lowest PSA value from the start of study therapy.
Time frame: 1 year, 2 years
Population: This analysis includes all patients that completed protocol therapy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abiraterone+Radiotherapy+ADT | PSA Nadir Value | Year 1 | 0.03 ng/mL |
| Abiraterone+Radiotherapy+ADT | PSA Nadir Value | Year 2 | 0.03 ng/mL |
Secondary
Safety and Tolerability
The number of patients experiencing an adverse event of at least grade 3 that is possibly, probably, or definitely related to study therapy per CTCAE version 4.0.
Time frame: 6 months
Population: This analysis includes all patients that completed protocol therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone+Radiotherapy+ADT | Safety and Tolerability | 12 Participants |
Secondary
Testosterone Recovery
Time to testosterone recovery
Time frame: up to 5 years
Population: Men with unfavorable prostate cancer (defined ad having a single high risk factor)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone+Radiotherapy+ADT | Testosterone Recovery | 9.2 months |
Secondary
Time to PSA Nadir
The median time in months to the lowest PSA value from the start of study therapy.
Time frame: 1 year
Population: This analysis includes all patients that completed protocol therapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone+Radiotherapy+ADT | Time to PSA Nadir | 8.9 months |