Prostate Cancer
Conditions
Keywords
prostate, metastatic, castrate resistant
Brief summary
The purpose of this research study is to determine if the addition of dutasteride to a regimen with abiraterone acetate and prednisone will improve on therapy in patients with castrate-resistant prostate cancer and metastatic disease. This study will also help determine the side effects of the study treatment and how often they occur.
Detailed description
Patients will receive abiraterone acetate and prednisone orally, once daily for 2 months (2 cycles) on an outpatient basis. At the start of cycle 3, dutasteride will be taken once daily. Patients will return to the clinic on Day 14 of the first 3 cycles for routine blood tests. Patients will come to the clinic every 12 weeks for a CT scan and/or x-ray of the chest, CT scan or MRI of the abdomen and pelvis, bone scan, and blood test for testosterone and other specialized blood test.
Interventions
DRUGAbiraterone acetate
DRUGDutasteride
DRUGPrednisone
Sponsors
Mary-Ellen Taplin, MD
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
* Diagnosis of adenocarcinoma of the prostate * Castrate resistant disease * Metastatic disease * Normal organ and marrow function * Subjects with partners of childbearing potential must be willing to use adequate methods of birth control
Exclusion criteria
* Uncontrolled intercurrent illness * Uncontrolled hypertension * Active or symptomatic viral hepatitis or chronic liver disease * History of pituitary or adrenal dysfunction * Clinically significant heart disease * History of a different malignancy unless disease-free for at least 5 years * Known brain metastasis * History of gastrointestinal disorders * Prior therapy with abiraterone acetate * HIV-positive individuals on antiretroviral therapy * Requirement for steroid use greater than the equivalent of 5 mg of prednisone daily * Atrial fibrillation or other cardiac arrhythmia requiring therapy * Thromboembolism in the last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Androgen Receptor (AR) Related Mutations | Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. | AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-Specific Antigen (PSA) Response | PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. | PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria. |
| Time to PSA Progression | PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. | Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of \>/=25% and \>/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of \>/=25% and \>/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response. |
| Best Overall Response | Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. | Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. |
| Change in Serum Levels of Testosterone | Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. | Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant. |
| Presence of AR Amplification | Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. | Presence of AR amplification was measured by established methods. |
| Change in Serum Androgen Levels | Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. | Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant. |
| Change in Circulating Tumor Cells (CTCs) Levels | Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. | CTCs were measured based on established methods. |
| Time to Progression (TTP) | Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint. | TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
Countries
United States
Participant flow
Recruitment details
Patients enrolled from September 2011 through October 2012
Participants by arm
| Arm | Count |
|---|---|
| Abiraterone + Prednisone + Dutasteride Abiraterone acetate + prednisone for two months, followed by abiraterone + prednisone + dutasteride in 28-day cycles until symptomatic or radiographic progression
Abiraterone acetate: 1000 mg orally, once per day
Dutasteride: 3.5 mg orally once per day
Prednisone: 5 mg orally once per day | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Abiraterone + Prednisone + Dutasteride |
|---|---|
| Age, Continuous | 61 years |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 38 |
| other Total, other adverse events | 38 / 38 |
| serious Total, serious adverse events | 12 / 38 |
Outcome results
Primary
Number of Participants With Androgen Receptor (AR) Related Mutations
AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.
Time frame: Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all patients evaluable for AR mutation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Number of Participants With Androgen Receptor (AR) Related Mutations | 1 Participants |
Secondary
Best Overall Response
Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Best Overall Response | 6 Participants |
Secondary
Change in Circulating Tumor Cells (CTCs) Levels
CTCs were measured based on established methods.
Time frame: Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: Data were not collected for this secondary endpoint.
Secondary
Change in Serum Androgen Levels
Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.
Time frame: Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Change in Serum Androgen Levels | 1.2 ng/dl |
Secondary
Change in Serum Levels of Testosterone
Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.
Time frame: Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Change in Serum Levels of Testosterone | 0.25 ng/dL |
Secondary
Presence of AR Amplification
Presence of AR amplification was measured by established methods.
Time frame: Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all evaluable patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Presence of AR Amplification | 10 Participants |
Secondary
Prostate-Specific Antigen (PSA) Response
PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.
Time frame: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Prostate-Specific Antigen (PSA) Response | 34 Participants |
Secondary
Time to Progression (TTP)
TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Time to Progression (TTP) | 11 Months |
Secondary
Time to PSA Progression
Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of \>/=25% and \>/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of \>/=25% and \>/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.
Time frame: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abiraterone + Prednisone + Dutasteride | Time to PSA Progression | 5 months |