IMAAGEN: Impact of Abiraterone Acetate in Prostate-Specific Antigen

Phase 2

Completed

Conditions: Prostate Cancer
Prostatic Neoplasm

Interventions: Drug: abiraterone acetate in combination with prednisone

Registration Number: NCT01314118

Lead Sponsor: Janssen Biotech, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 131

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
001	abiraterone acetate in combination with prednisone	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Time to Radiographic Evidence of Disease Progression (TTRP)	Maximum up to Month 30.5	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.
Time to Prostate-Specific Antigen (PSA) Progression	Maximum up to Month 30.5	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.
Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) Levels After 3 Cycles of Treatment	End of Cycle 3 (Approximately Month 3)	Percentage of participants with greater than or equal to 50 percent decrease in PSA levels was assessed. Decrease in PSA levels represented improvement.