Back to resultsA Safety and Efficacy Study of Abiraterone Acetate in Participants With Prostate Cancer Who Have Failed Hormone Therapy
Primary Purpose
Prostatic Neoplasms
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Abiraterone acetate
Abiraterone acetate MTD
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasms focused on measuring Abiraterone acetate, CB7630, Prostatic neoplasms, Hormone refractory prostate cancer, Castration resistant prostate cancer, Castration refractory prostate cancer
Eligibility Criteria
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- Participants who were withdrawn from anti-androgen therapy less than 6 months prior to inclusion in the study require one PSA higher than the last pre-withdrawal PSA or 2 increases in PSA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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Abiraterone acetate
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants With Confirmed Prostate Specific Antigen (PSA) Response at Week 12
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.
Secondary Outcome Measures
Number of Participants With Objective Tumor 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 Prostate Specific Antigen (PSA) 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.
Duration of Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Time to Disease Progression
Disease progression was defined as greater than 25 percent increase in sum of longest diameter of target lesions compared to baseline.
Overall Survival
Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Full Information
NCT ID
NCT00473512
First Posted
May 11, 2007
Last Updated
February 27, 2014
Sponsor
Cougar Biotechnology, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00473512
Brief Title
A Safety and Efficacy Study of Abiraterone Acetate in Participants With Prostate Cancer Who Have Failed Hormone Therapy
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
November 2005 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cougar Biotechnology, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The 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).
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms
Keywords
Abiraterone acetate, CB7630, Prostatic neoplasms, Hormone refractory prostate cancer, Castration resistant prostate cancer, Castration refractory prostate cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Abiraterone acetate
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Abiraterone acetate
Other Intervention Name(s)
CB7630
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Abiraterone acetate MTD
Other Intervention Name(s)
CB7630
Intervention Description
Abiraterone acetate MTD orally for 12 cycles (28 day each).
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 0.5 mg orally will be given (If participants have disease progression) daily up to 12 cycles.
Primary Outcome Measure Information:
Title
Number of Participants With Confirmed Prostate Specific Antigen (PSA) Response at Week 12
Description
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.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Number of Participants With Objective Tumor Response
Description
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.
Time Frame
Baseline up to end of study (1160 days)
Title
Duration of Prostate Specific Antigen (PSA) Response
Description
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.
Time Frame
Baseline up to end of study (1160 days)
Title
Duration of Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
Description
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.
Time Frame
Baseline up to end of study (1160 days)
Title
Time to Disease Progression
Description
Disease progression was defined as greater than 25 percent increase in sum of longest diameter of target lesions compared to baseline.
Time Frame
Baseline up to end of study (1160 days)
Title
Overall Survival
Description
Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.
Time Frame
Baseline up to end of study (1160 days)
Other Pre-specified Outcome Measures:
Title
Serum Blood Levels of Testosterone
Description
Concentration of testosterone in blood was measured in nanogram per deciliter (ng/dL).
Time Frame
Baseline, Cycle 2 (within 3 days prior to Day 29)
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to 30 days after the last dose of study medication
Title
Serum Blood Levels of Testosterone Precursors
Description
Concentration of Cortisol, Aldosterone, Corticosterone, 11-Deoxycortisol, Deoxycorticosterone and Dehydroepiandrostenedione Sulphate (DHEA-S) in blood was measured in nanogram per deciliter (ng/dL).
Time Frame
Baseline, Cycle 2 (within 3 days prior to Day 29)
Title
Time to Prostate Cancer Pain Progression
Description
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.
Time Frame
Baseline up to 12 cycles
Title
Number of Participants With Change From Baseline in Biochemical Bone Markers
Time Frame
Baseline, Cycle 2, 4, 8, 12
Title
Mean Plasma Concentration of Abiraterone
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Title
Maximum Observed Plasma Concentration (Cmax) of Abiraterone
Description
The Cmax is defined as maximum observed analyte concentration.
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone
Description
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.
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Abiraterone
Description
Area under the plasma concentration time-curve from time zero to the last quantifiable concentration (AUClast).
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Title
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Abiraterone
Description
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 - ∞).
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Title
Plasma Decay Half-Life (t1/2) of Abiraterone
Description
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Title
Time to Last Quantifiable Plasma Concentration (Tlast) of Abiraterone
Description
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.
Time Frame
Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cougar Biotechnology Clinical Trial
Organizational Affiliation
Cougar Biotechnology, Inc.
Official's Role
Study Director
Facility Information:
City
Sutton
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.cancer.gov/
Description
NATIONAL CANCER INSTITUTE
URL
http://www.nlm.nih.gov/medlineplus/prostatecancer.html
Description
PROSTATE CANCER
Learn more about this trial
A Safety and Efficacy Study of Abiraterone Acetate in Participants With Prostate Cancer Who Have Failed Hormone Therapy
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