Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Trial of Abiraterone Acetate Combined With Dutasteride With Correlative Assessment of Tumor Androgen Levels and Androgen Receptor Sequence and Signaling at Baseline and at Progression

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone acetate
* Drug: Dutasteride
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone+prednisone+dutasteride<br>Abiraterone acetate 1000mg orally once per day + prednisone 5mg orally once per day for two months, followed by abiraterone 1000mg orally once per day + prednisone 5mg orally once per day + dutasteride 3.5mg orally once per day in 28-day cycles until symptomatic or radiographic progression | Drug: Abiraterone acetate<br> <br> * Other names: CB7630;Drug: Dutasteride<br> <br> * Other names: Avodart;Drug: Prednisone<br> <br> * Other names: Corticosteroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 
| 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. | 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 | 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. | 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. | 
| 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. | 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. | 
| 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. | 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. | 
| Presence of AR Amplification | Presence of AR amplification was measured by established methods. | 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. | 
| Change in Serum Androgen Levels | Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant. | 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. | 
| Change in Circulating Tumor Cells (CTCs) Levels | CTCs were measured based on established methods. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate, metastatic, castrate resistant