Title
A Safety and Efficacy Study of Abiraterone Acetate in Participants With Prostate Cancer Who Have Failed Hormone Therapy
A Phase I/II Open Label Study of the 17α-Hydroxylase/ C17,20 Lyase Inhibitor, Abiraterone Acetate in Patients With Prostate Cancer Who Have Failed Hormone Therapy
Phase
Phase 1/Phase 2Lead Sponsor
Cougar BiotechnologyStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Prostatic NeoplasmsIntervention/Treatment
urea abiraterone ...Study Participants
54The purpose of this study is to determine the maximum tolerated dose and evaluate the safety, tolerability, and activity at the recommended dose (maximum tolerated dose [MTD]) of abiraterone acetate (also known as CB7630) in participants with hormone refractory prostate (gland that makes fluid that aids movement of sperm) cancer (HRPC).
This is an open-label (all people know the identity of the intervention) study to evaluate the safety, tolerability, and recommended dose of abiraterone acetate taken orally (by mouth), once daily in participants with HRPC. The study will consist of a dose escalation stage (Phase 1) that will be conducted to determine the MTD of abiraterone and an activity evaluation stage (Phase 2) to evaluate the activity of abiraterone in participants with HRPC. Escalated doses of abiraterone (starting at 250 milligram [mg] up to a maximum of 2000 mg) will be given for 28-day treatment periods to determine the MTD. Participants will be given MTD of abiraterone for up to 12 cycles (28 day each) in Phase 2 of the study. Participants' safety will be monitored throughout the study.
Abiraterone 250 mg (1 capsule) up to 2000 mg (8 capsules) once daily, each dose will be tested in sequential order for 28 days to determine the MTD.
Abiraterone acetate MTD orally for 12 cycles (28 day each).
Dexamethasone 0.5 mg orally will be given (If participants have disease progression) daily up to 12 cycles.
Abiraterone acetate 250 mg up to a maximum of 2000 mg capsules will be given orally daily for 28-day treatment period to determine the MTD in Phase 1 of the study. Participants will receive MTD of abiraterone acetate for 12 cycles (28 day each) in Phase 2 of the study. Dexamethasone 0.5 mg will be given orally (If participants have disease progression) daily up to 12 cycles.
Inclusion Criteria: Histologically (pertaining to the disease status of body tissues or cells) documented adenocarcinoma of the prostate, clinically refractory (not responding to treatment) or resistant to hormone therapy, as documented by progression following at least one hormonal therapy Prostate specific antigen (PSA) evidence for progressive prostate cancer Participants who were withdrawn from anti-androgen therapy less than 6 months prior to inclusion in the study require one PSA higher than the last pre-withdrawal PSA or 2 increases in PSA documented after the post-withdrawal nadir(value) greater than or equal to 4 weeks from treatment withdrawal if treated with flutamide and greater than or equal to 6 weeks if treated with bicalutamide or nilutamide Eastern Cooperative Oncology Group (ECOG) performance status score equal to 0 or 1 Life expectancy of greater than or equal to12 week Exclusion Criteria: Participants with central nervous system (the brain and spinal cord) disease and/or brain metastases No currently active second malignancy (cancer or other progressively enlarging and spreading tumor) other than non-melanoma skin cancer Myocardial infarction within the 6 months prior to start of study No active or uncontrolled autoimmune disease (disorder in which a person's immune system attacks parts of his or her own body) that may require corticosteroid therapy during protocol treatment Major surgery or significant traumatic injury within 4 weeks of start of study
| Event Type | Organ System | Event Term | 250 mg/Day | 500 mg/Day | 750 mg/Day | 1000 mg/Day | 2000 mg/Day |
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The PSA response was measured according to PSA working group (PSAWG) criteria. All participants achieving a fall in PSA of greater than 50 percent from baseline, which has been confirmed by a second measurement at least 4 weeks after initial documentation, fulfill criteria for confirmed PSA response.
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response.
Duration of PSA response in participants on abiraterone acetate therapy was measured as the duration between PSA 50 percent decline date and PSA progression date as defined by the PSAWG criteria.
Number of participants with objective response based on assessment of confirmed CR or confirmed PR according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to 30 percent decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response.
Disease progression was defined as greater than 25 percent increase in sum of longest diameter of target lesions compared to baseline.
Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Concentration of testosterone in blood was measured in nanogram per deciliter (ng/dL).
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Concentration of Cortisol, Aldosterone, Corticosterone, 11-Deoxycortisol, Deoxycorticosterone and Dehydroepiandrostenedione Sulphate (DHEA-S) in blood was measured in nanogram per deciliter (ng/dL).
The time from start of study treatment to the development/worsening of pain due to prostate cancer requiring one or more of the following treatments: 1- Opioid therapy (therapy with morphine like medicines for 10 out of 14 consecutive days); 2- Glucocorticoid therapy; 3- Initiation of >= 5 mg of prednisolone for 10 out of 14 consecutive days; 4- Radionuclide therapy; 5- Radiation therapy (x-ray or cobalt treatment); 6- Chemotherapy (treatment of disease by chemical agents). Participants who do not experience prostate cancer pain were censored on their last day on study. Time to prostate cancer pain progression was measured by Kaplan-Meier method.
The Cmax is defined as maximum observed analyte concentration.
The Tmax is defined as actual sampling time to reach maximum observed plasma concentration. The analyte concentration associated with Tmax is referred to as Cmax.
Area under the plasma concentration time-curve from time zero to the last quantifiable concentration (AUClast).
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
The actual sampling time of last measurable (non-below the limit of quantification [BQL]) analyte concentration. The analyte concentration associated with Tlast is referred to as Clast.
