IMAAGEN: Impact of Abiraterone Acetate in Prostate-Specific Antigen

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to show that abiraterone acetate plus prednisone added to the current standard of care, gonadotropin-releasing hormone (GnRH) decreases prostate specific antigen (PSA) and prolongs the time until it is evident that the cancer has grown. Additionally, safety information about abiraterone acetate in combination with prednisone will be collected. This will include looking at what side effects occur, how often they occur, and for how long they last.

Detailed Description
-----------------
This is a Phase 2, prospective, multicenter, open-label, single-arm study of abiraterone acetate plus prednisone in men with non-metastatic, castration-resistant prostate cancer (CRPC) who have a rising PSA despite castrate levels of testosterone. The study consists of Screening Phase (up to 4 weeks), Core Study Treatment Phase (comprised of six 28-day cycles), a Pre-metastatic Disease Follow-up Phase, an Optional Drug Holiday Phase; and a 30-day Safety Follow-up Visit. Each treatment cycle will last 28 days. Participating participants will receive study agents (Abiraterone acetate 1000 mg/day plus prednisone 5 mg/day, orally) continually during the study. If the partcipants elects to participate in the Optional Drug Holiday Phase, participants will discontinue abiraterone acetate plus prednisone and ADT. Participants will have the option to return to study medication during the first year of the Optional Drug Holiday Phase if there is evidence of rising PSA but no metastasis based on study imaging. If participants do no elect to participate, they will continue with the core study treatment as per protocol. The study will end when all participated participants have disease progression or end of the 2-year period (if participants participated in the Optional Drug Holiday Phase). Participants will be required to return to the study site 30 days after receiving the last dose of abiraterone acetate for safety follow-up.

Official Title
-----------------
A Multicenter, Open-label, Single-arm, Phase 2 Study of Abiraterone Acetate Plus Prednisone in Subjects With Advanced Prostate Cancer Without Radiographic Evidence of Metastatic Disease

Conditions
-----------------
Prostatic Neoplasm, Prostate Cancer

Intervention / Treatment
-----------------
* Drug: abiraterone acetate in combination with prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Major Inclusion Criteria: Be a male >= 18 years of age Have adenocarcinoma of the prostate Currently receiving continuous treatment with Gonadotropin-releasing hormone (GnRH) monotherapy for at least 6 months before or have undergone surgical removal of the testicles Serum testosterone of < 50 ng/dL(< 2.0 nM) Have rising PSA defined as a PSA of >= 10 ng/mL obtained at screening or PSADT of ≤ 10 months with the first of the 3 consecutive PSA values used to calculate PSADT ≥ 2.0 ng/mL Have an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Be capable of swallowing study agents whole as a tablet Be willing/able to adhere to the prohibitions and restrictions specified in this protocol Major Exclusion Criteria: Have prior or current evidence of local disease progression or metastatic disease as defined by modified response evaluation criteria in solid tumors (RECIST) criteria Have received chemotherapy for treatment of castrate-resistant prostate cancer; however, if a patient received chemotherapy in an adjuvant setting, prior to having CRPC, for castrate-sensitive prostate cancer, the patient is still eligible Are currently receiving any antiandrogen therapy (eg, bicalutamide, flutamide, or nilutamide). If previously treated with antiandrogen therapy, there must be documentation of at least 2 consecutive rising PSA values at least 2 weeks apart obtained prior to screening If previously treated with flutamide, at least 1 of the PSA values must be obtained 4 weeks or more after flutamide discontinuation. If previously treated with bicalutamide or nilutamide, at least 1 of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation Have previously received agents having any CYP17 inhibitory activity for the treatment of prostate cancer, such as ketoconazole Have previously received aminoglutethimide Have an active infection or other medical condition that would contraindicate prednisone use Have uncontrolled hypertension Have active hepatitis or chronic liver disease Have clinically significant heart disease Have poorly controlled diabetes Have received an investigational therapeutic within 30 days of screening Have partners of childbearing potential and are not willing 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 1 week after last dose of abiraterone acetate. Individuals with a history of a non-prostate malignancy are ineligible for this study with the following exceptions. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: basal cell or squamous cell carcinoma of the skin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>abiraterone acetate in combination with prednisone Abiraterone acetate will be taken as 4 x 250 mg tablets by mouth (PO) once daily. Prednisone will be taken as 2 x 2.5 mg tablets PO once daily. | Drug: abiraterone acetate in combination with prednisone<br>* Abiraterone acetate will be taken as 4 x 250 mg tablets by mouth (PO) once daily. Prednisone will be taken as 2 x 2.5 mg tablets PO once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) During the Core Study | Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed. | End of core study visit (Approximately at Month 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Radiographic Evidence of Disease Progression (TTRP) | Time to radiographic evidence of disease progression is defined as the time interval from the date of enrollment (Day 1) to the date of disease progression. A participant was considered as progressed by bone scan if: 1) The appearance of greater than or equal to (>=) 2 new lesions, and, following the first assessment, a confirmatory scan performed 6 or more weeks later that shows a minimum of 2 or more additional new lesions, 2) If >=2 new lesions are seen on scans following the first assessment, the confirmation is still required after 6 weeks; however, 2 addition lesions are not required to confirm progression, and 3) The date of progression is the date of the first scan that shows the changes. | Maximum up to Month 30.5 | 
| Time to Prostate-Specific Antigen (PSA) Progression | Time to PSA progression is defined as the time interval from the date of enrollment (Day 1) to the date of first evidence of PSA progression. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase and an absolute increase of 2 nanogram (ng)/milliliter (mL) or more, which is confirmed by a second value obtained in 3 or more weeks. | Maximum up to Month 30.5 | 
| Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) Levels After 3 Cycles of Treatment | Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed. Decrease in PSA levels represented improvement. | End of Cycle 3 (Approximately Month 3) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
abiraterone acetate, prednisone, zytiga