IMAAGEN: Impact of Abiraterone Acetate in Prostate-Specific Antigen

• The proportion of subjects with a >= 50% reduction in PSA levels after 3 cycles of treatment and absolute PSA reduction [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
• The proportion of subjects with evidence of radiographic disease progression over time [ Time Frame: Approximately or an average of 24 months. Disease progression is measured throughout the study duration ] [ Designated as safety issue: No ]
• Time to radiographic evidence of disease progression [ Time Frame: Approximately or an average of 24 months. Disease progression is measured throughout the study duration ] [ Designated as safety issue: No ]

• The proportion of subjects with a = 50% reduction in PSA levels after 3 cycles of treatment and absolute PSA reduction [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
• The proportion of subjects with evidence of radiographic disease progression over time [ Time Frame: Approximately or an average of 24 months. Disease progression is measured throughout the study duration ] [ Designated as safety issue: No ]
• Testosterone over time [ Time Frame: Approximately 3 and 6 months ] [ Designated as safety issue: No ]
• Time to radiographic evidence of disease progression [ Time Frame: Approximately or an average of 24 months. Disease progression is measured throughout the study duration ] [ Designated as safety issue: No ]
• Time to PSA (Prostate Specific Antigen) progression [ Time Frame: Approximately or an average of 24 months. PSA levels are measured throughout the study duration ] [ Designated as safety issue: No ]

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.

This is a Phase 2, prospective, multicenter, open-label (both the patient and investigator will know what treatment is taken), single-arm study of abiraterone acetate plus prednisone in patients with non-metastatic (has not spread in the body), castration-resistant prostate cancer (CRPC) who have a rising PSA despite castrate levels of testosterone. This study has 4 phases: Screening Phase (up to 28 Days); Core Study Treatment Phase (Treatment-Cycle 1-6); Follow-up Phase (Treatment-Cycle 7- until disease progression); and an Extension Phase (after the end of the official study). Each treatment cycle will last 28 days (about a month). Your participation in the study will include a screening period of up to 28 days, which allows the doctor to assess whether or not you qualify for the study. There is a Core Treatment Phase where study medication is taken for six treatment cycles (about 6 months). There is a Follow-up Phase where study medication will continue to be taken until your prostate cancer progresses, or you have unacceptable toxicities or this phase of the study ends (approximately 18 months). If your prostate cancer progresses before the end of the follow-up phase, you will not be given further study medication. However, the study doctor will contact you about every 2 months to record any new therapy for prostate cancer you are taking until the end of the follow-up phase. If for some reason you stop study medication before the end of the follow-up phase, the study doctor will contact you about every 2 months to record any new therapy for prostate cancer you are taking until the end of the follow-up phase or until your prostate cancer progresses, whichever happens first. You will be required to return to the study site 30 days after receiving your last dose of abiraterone acetate for safety follow-up. You may be in the study for about 24 months. Four abiraterone acetate tablets should be taken by mouth [PO] at least 2 hours after eating & no food should be eaten for at least 1 hour afterward. Two (2.5 mg) prednisone tablets will be taken PO once daily, preferably with food. Patients may continue abiraterone acetate until disease progression, until unacceptable toxicities develop, until abiraterone acetate becomes commercially available for the indication being studied, or until the sponsor determines it is necessary to stop the study.

• Prostate Cancer
• Prostatic Neoplasm

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