Prostatic Neoplasms
Conditions
Keywords
Metastatic Castration-Resistant Prostate Cancer, CRPC, Abiraterone Acetate, CB7630
Brief summary
This is a phase 3 study to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC) who have failed one or two chemotherapy regimens. At least one of the previous chemotherapies must have contained docetaxel.
Detailed description
Abiraterone acetate is a steroidal irreversible inhibitor of CYP17 (17α hydroxylase/C17, 20-lyase), blocking 2 important enzymatic activities in the synthesis of testosterone. The goal of this study is to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC) who have failed one or two chemotherapy regimens, one of which contains docetaxel. All patients involved in the study will be randomized (assigned by chance) into one of two arms and will not know what study drug is being given to them. Study drug randomization allocation will be 2:1 (abiraterone acetate: placebo). The study will be conducted in the United States, Canada, Australia, and the EU. The study will consist of screening, treatment, and follow-up. In this study, patients will receive study treatment (abiraterone acetate or placebo) plus prednisone until progression of clinical disease. Follow-up will continue until patient dies, is lost to follow-up, or withdraws informed consent. After providing written informed consent, patients will have screening procedures completed to determine eligibility. Safety evaluations at the screening procedure will include a physical examination, vital signs, and clinical blood laboratory tests, ECG, radiographs, urine tests, and recording of any adverse events including details of current prostate cancer symptoms. Patients will be asked 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 13 weeks after last study drug administration. Study medication, abiraterone acetate,is an oral (by mouth) medication to be administered as four (4) 250mg abiraterone acetate tablets or 4 placebo tablets to be taken at least one hour before or two hours after a meal anytime up to 10PM everyday. Prednisone will be administered as 5mg orally twice a day for both groups. Each cycle will be 28 days. Study treatment will continue until disease progression as determined by investigator or when the patient meets criteria for withdrawal from study.
Interventions
DRUGPlacebo
Four tablets once daily until disease progression
DRUGAbiraterone acetate
Four 250-mg tablets once daily until disease progression
5 mg twice daily until disease progression
Sponsors
Cougar Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic Castration-Resistant Prostate Cancer Progression after one or two prior cytotoxic chemotherapies * At least one chemotherapy must have contained docetaxel * Eastern Cooperative Oncology Group (ECOG) Performance Status \<= 2 * Medical or surgical castration with testosterone \< 50 ng/dL * Adequate bone marrow, hepatic and renal function * Potassium \>= 3.5 mmol/L * Able to swallow the study drug whole as a tablet * Informed Consent
Exclusion criteria
* More than two prior cytotoxic chemotherapy regimens * Prior Ketoconazole for prostate cancer * Prior abiraterone acetate or other CYP17 inhibitor or investigational agents targeting the androgen receptor for prostate cancer * Uncontrolled hypertension * Active or symptomatic viral hepatitis or chronic liver disease * History of pituitary or adrenal dysfunction * Clinically significant heart disease * Other malignancy * Known brain metastasis * GI disorder affecting absorption * Not willing to use contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 60 months | Overall survival is defined as the time interval from the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Prostate-Specific Antigen Progression According to Prostate Specific Antigen Working Group Criteria | Up to 12 months | The time interval from the date of randomization to the date of the prostate-specific antigen (PSA) progression as defined in the protocol-specific Prostate Specific Antigen Working Group (PSAWG) criteria, namely, a PSA level of at least 5 ng/ml that has risen on at least 2 successive occasions, at least 2 weeks apart. |
| Number of Patients Achieving a Prostate-Specific Antigen Decline >=50% | Up to 12 months | A prostate-specific antigen (PSA) response was defined as a \>=50% decline from baseline. |
| Radiographic Progression-free Survival | Up to 11 months | Radiographic progression-free survival is based on imaging studies according to modified Response Evaluation Criteria in Solid Tumors (RECIST): baseline lymph node size must be \>=2.0 cm to be considered a target lesion; progression on bone scans with \>=2 new lesions not consistent with tumor flare, confirmed on a second scan \>=6 weeks later that shows \>=1 additional new lesion. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Hungary, Ireland, Netherlands, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone Acetate Abiraterone acetate plus prednisone/prednisolone administered as four 250 mg tablets of abiraterone acetate once daily plus 5 mg prednisone/5 mg prednisolone twice daily until disease progression. | 797 |
| Placebo Placebo plus prednisone/prednisolone | 398 |
| Total | 1,195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 655 | 335 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Withdrawal by Subject | 22 | 5 |
Baseline characteristics
| Characteristic | Abiraterone Acetate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 69.1 years STANDARD_DEVIATION 8.4 | 68.9 years STANDARD_DEVIATION 8.61 | 69 years STANDARD_DEVIATION 8.46 |
| Region of Enrollment Australia | 69 participants | 35 participants | 104 participants |
| Region of Enrollment Austria | 11 participants | 1 participants | 12 participants |
| Region of Enrollment Belgium | 32 participants | 11 participants | 43 participants |
| Region of Enrollment Canada | 97 participants | 57 participants | 154 participants |
| Region of Enrollment France | 57 participants | 33 participants | 90 participants |
| Region of Enrollment Germany | 26 participants | 12 participants | 38 participants |
| Region of Enrollment Hungary | 5 participants | 2 participants | 7 participants |
| Region of Enrollment Italy | 21 participants | 12 participants | 33 participants |
| Region of Enrollment Netherlands | 4 participants | 2 participants | 6 participants |
| Region of Enrollment Republic of Ireland | 7 participants | 7 participants | 14 participants |
| Region of Enrollment Spain | 13 participants | 3 participants | 16 participants |
| Region of Enrollment United Kingdom | 119 participants | 61 participants | 180 participants |
| Region of Enrollment United States | 336 participants | 162 participants | 498 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 797 Participants | 398 Participants | 1195 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 766 / 791 | 381 / 394 | 57 / 67 |
| serious Total, serious adverse events | 365 / 791 | 175 / 394 | 29 / 67 |
Outcome results
Primary
Overall Survival
Overall survival is defined as the time interval from the date of randomization to the date of death from any cause.
Time frame: Up to 60 months
Population: Analysis was performed on the Intent-to-Treat (ITT) population. The ITT population is composed of all patients randomized into the study and who will be classified according to their assigned teatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate | Overall Survival | 450.0 Days |
| Placebo | Overall Survival | 332.0 Days |
p-value: <0.000195% CI: [0.543, 0.768]Log Rank
Secondary
Number of Patients Achieving a Prostate-Specific Antigen Decline >=50%
A prostate-specific antigen (PSA) response was defined as a \>=50% decline from baseline.
Time frame: Up to 12 months
Population: Analysis was performed on the Intent-to-Treat (ITT) population. The ITT population is composed of all patients randomized into the study and who will be classified according to their assigned teatment group, regardless of the actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abiraterone Acetate | Number of Patients Achieving a Prostate-Specific Antigen Decline >=50% | 232 Participants |
| Placebo | Number of Patients Achieving a Prostate-Specific Antigen Decline >=50% | 22 Participants |
p-value: <0.00195% CI: [3.459, 8.018]Chi-squared
Secondary
Radiographic Progression-free Survival
Radiographic progression-free survival is based on imaging studies according to modified Response Evaluation Criteria in Solid Tumors (RECIST): baseline lymph node size must be \>=2.0 cm to be considered a target lesion; progression on bone scans with \>=2 new lesions not consistent with tumor flare, confirmed on a second scan \>=6 weeks later that shows \>=1 additional new lesion.
Time frame: Up to 11 months
Population: Analysis was performed on the Intent-to-Treat (ITT) population. The ITT population is composed of all patients randomized into the study and who will be classified according to their assigned teatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate | Radiographic Progression-free Survival | 171.0 Days |
| Placebo | Radiographic Progression-free Survival | 110.0 Days |
p-value: <0.000195% CI: [0.585, 0.776]Log Rank
Secondary
Time to Prostate-Specific Antigen Progression According to Prostate Specific Antigen Working Group Criteria
The time interval from the date of randomization to the date of the prostate-specific antigen (PSA) progression as defined in the protocol-specific Prostate Specific Antigen Working Group (PSAWG) criteria, namely, a PSA level of at least 5 ng/ml that has risen on at least 2 successive occasions, at least 2 weeks apart.
Time frame: Up to 12 months
Population: Analysis was performed on the Intent-to-Treat (ITT) population. The ITT population is composed of all patients randomized into the study and who will be classified according to their assigned teatment group, regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone Acetate | Time to Prostate-Specific Antigen Progression According to Prostate Specific Antigen Working Group Criteria | 309.0 Days |
| Placebo | Time to Prostate-Specific Antigen Progression According to Prostate Specific Antigen Working Group Criteria | 200.0 Days |
p-value: <0.000195% CI: [0.462, 0.728]Log Rank