IMAAGEN: Impact of Abiraterone Acetate in Prostate-Specific Antigen

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer; Prostatic Neoplasm
• Intervention / Treatment: Drug: abiraterone acetate in combination with prednisone

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.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Homewood, Alabama, United States
    • Huntsville, Alabama, United States
  • Arizona
    • Tucson, Arizona, United States
  • California
    • Los Angeles, California, United States
    • San Diego, California, United States
    • San Francisco, California, United States
  • Colorado
    • Aurora, Colorado, United States
    • Denver, Colorado, United States
  • Florida
    • Aventura, Florida, United States
    • Orange City, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Evanston, Illinois, United States
    • Galesburg, Illinois, United States
    • Glenview, Illinois, United States
    • Melrose Park, Illinois, United States
  • Indiana
    • Fort Wayne, Indiana, United States
    • Jeffersonville, Indiana, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Maryland
    • Baltimore, Maryland, United States
    • Rockville, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Lansing, Michigan, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Jersey
    • Lawrenceville, New Jersey, United States
  • New York
    • Albany, New York, United States
    • Brooklyn, New York, United States
    • Buffalo, New York, United States
    • Garden City, New York, United States
    • New York, New York, United States
    • Poughkeepsie, New York, United States
    • Staten Island, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
    • Raleigh, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
  • Pennsylvania
    • Lancaster, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Greenville, South Carolina, United States
    • Myrtle Beach, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Arlington, Texas, United States
    • Houston, Texas, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; 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; 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.

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)

Collaborators and Investigators

• Sponsor: Janssen Biotech, Inc.
• Investigators: Study Director: Janssen Services, LLC. Clinical Trial, Janssen Biotech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2011
• Primary Completion (Actual): December 24, 2013
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: March 4, 2011
• First Submitted That Met QC Criteria: March 10, 2011
• First Posted (Estimated): March 14, 2011

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: abiraterone acetate; prednisone; zytiga
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: CR017932; Protocol 212082PCR2005 (Other Identifier: Janssen Biotech Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No