Back to resultsA Phase 2 Study to Evaluate Safety and Efficacy of Abiraterone Acetate in Male Participants With Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Abiraterone
Leuprolide
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate cancer, Abiraterone acetate, Leuprolide acetate, Prednisone, CB7630, Testosterone
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- At least three core biopsies positive for prostate cancer (a minimum of 6 core biopsies must be obtained at baseline). A prostate biopsy within 6 months from Screening is allowed for entry requirements
- At least one of the following features: prostate specific antigen (PSA) greater than (>) 10 nanogram per milliliter (ng/ml); PSA velocity >2 ng/ml per /year (defined as a rise in PSA of >2 ng/ml in the preceding 12 month period); Gleason score greater than or equal to (>=) 7 (4+3); Gleason score 6 if either PSA >=10 ng/ml or PSA velocity >=2 ng/ml/year
- Serum testosterone >200 nanogram/deciliter
- Participant and urologist must agree that participant is suitable for prostatectomy
Exclusion Criteria:
- Serious or uncontrolled co-existent, non-malignant disease, including active and uncontrolled infection
- Abnormal liver function consisting of any of the following: serum bilirubin >= 1.5 * upper limit of normal (ULN); aspartate aminotransferase or alanine aminotransferase >=2.5 * ULN
- Uncontrolled hypertension within the Screening period (systolic blood pressure >= 160 millimeter of mercury [mmHg] or diastolic BP >= 95 mmHg)
- Requirement for corticosteroids greater than the equivalent of 5 milligram of prednisone daily
- Participants with active or symptomatic viral hepatitis or chronic liver disease or clinically significant heart disease or as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50 percent at Baseline or history of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug or history of pituitary or adrenal dysfunction
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Abiraterone plus leuprolide plus prednisone
Leuprolide then abiraterone plus leuprolide plus prednisone
Arm Description
Abiraterone acetate tablets will be administered orally at a total dose of 1000 milligram (mg) per day up to Week 24. Leuprolide acetate will be administered at a dose of 22.5 mg (dose adjusted as per Investigator's discretion) as intramuscular injection (injection of a substance into a muscle) once every 12 weeks up to Week 24. Prednisone tablets will be administered orally as 5 mg once daily for 24 weeks.
Leuprolide acetate will be administered at a dose of 22.5 mg as intramuscular injection once every 12 weeks up to Week 24. From Week 13 to 24, abiraterone acetate tablets will be administered orally at a total dose of 1000 mg per day with prednisone tablets administered orally as 5 mg once daily.
Outcomes
Primary Outcome Measures
Testosterone Concentration in Prostate Tissue
Testosterone is a potent androgen (a hormone that promotes the development and maintenance of male characteristics) and major product secreted by cells in the testis and produced in the adrenal glands and by prostate cancers. Abiraterone acetate affects sources of testosterone in the body (ie, adrendal gland and prostate tumor). Testosterone concentration was measured in prostate tissues after exposure to study treatments at Week 12.
Dihydrotestosterone (DHT) Concentration in Prostate Tissue
The DHT is a potent androgenic metabolite of testosterone and the concentration of DHT was measured in prostate tissues after exposure to study treatments at Week 12.
Secondary Outcome Measures
Testosterone and Dihydrotestosterone (DHT) Concentration in Prostate Tissue
Testosterone is a potent androgen (a hormone that promotes the development and maintenance of male characteristics) and major product secreted by cells in the testis and produced in the adrenal glands and by prostate cancers. Dihydrotestosterone (DHT) is a potent androgenic metabolite of testosterone. Testosterone and DHT concentration was measured in prostate tissues after exposure to study treatments at Week 24.
Androstenedione and Dehydroepiandrosterone (DHEA) Concentrations in Prostate Tissue
Androstenedione is a steroid (a group of polycyclic compounds closely related biochemically to terpenes, for example, cholesterol, numerous hormones), that is produced in the testis, ovary and the adrenal cortex, and depending on the tissue type, androstenedione can serve as a precursor to testosterone, estrone and estradiol. The DHEA is a major steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Androstenedione and DHEA concentration was measured in prostate tissues at Week 12 and 24.
Serum Levels of Androgens
Serum concentrations of testosterone, DHT, androsterone, DHEA, DHEA-Sulfate, DHEA-Glucuronide and delta-4-androstenedione were measured at Weeks 12 and 24.
Percentage of Participants With Prostate-specific Antigen (PSA) Response
The PSA response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criterion which is, percentage of participants with PSA less than or equal to 0.2 nanogram/milliliter at Weeks 12 and 24 after androgen deprivation.
Percentage of Participants With Pathologic Complete Response (CR)
Complete response is defined as a disappearance of all target lesions and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criterion.
Number of Participants With Tumor Expression of Androgen Receptor (AR) Regulated Genes at Week 24
Tumor expression of AR regulated genes determined by real-time polymerase chain reaction (RT PCR). PCR is an in vitro method for producing large amounts of specific deoxyribonucleic acid (DNA) or ribonucleic acid fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). RT PCR is a method used for detecting the amplified DNA products from the PCR as they accumulate instead of at the end of the reaction.
Correlation Between Molecular and Protein Expression With Intracellular Androgen Levels and Pathologic Response to Study Treatment
Molecular and protein expression was correlated with intracellular androgen levels and pathologic response to study treatment.
Full Information
NCT ID
NCT00924469
First Posted
June 17, 2009
Last Updated
March 6, 2013
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT00924469
Brief Title
A Phase 2 Study to Evaluate Safety and Efficacy of Abiraterone Acetate in Male Participants With Prostate Cancer
Official Title
A Phase 2 Open-Label, Randomized, Multi-center Study of Neoadjuvant Abiraterone Acetate (CB7630) Plus Leuprolide Acetate and Prednisone Versus Leuprolide Acetate Alone in Men With Localized High Risk Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate safety and efficacy of abiraterone acetate plus leuprolide acetate and prednisone, versus leuprolide acetate alone in male participants with prostate cancer (a disease in which cells in the prostate gland become abnormal and start to grow uncontrollably, forming tumors) who are suitable candidates for prostatectomy (surgery to remove all or part of the prostate gland).
Detailed Description
This is an open-label (all people know the identity of the intervention), randomized (the study drug is assigned by chance), and multi-center (conducted in more than one center) study of abiraterone in male participants with prostate cancer. The duration of study will be approximately 24-32 weeks per participant. The study consists of 4 parts: Screening (that is, 30 days before study commences on Day 1); Treatment (abiraterone acetate 1000 milligram per day or leuprolide acetate as 22.5 milligram intramuscular injection [injection of a substance into a muscle] or prednisone 5 mg once daily); Prostatectomy (Week 24); and Follow-up ( 4-8 weeks after prostatectomy). Participants will receive either abiraterone, leuprolide and prednisone for 24 weeks (that is, Group 1) or leuprolide once every 12 weeks up to Week 24 then abiraterone and prednisone from Week 13 to 24 (that is, Group 2). All the eligible participants will be randomly assigned to 1 of the 2 treatment groups. Efficacy will be evaluated primarily through the concentrations of testosterone and dihydrotestosterone from prostate tissues at Week 12. Participants' safety will be monitored throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate cancer, Abiraterone acetate, Leuprolide acetate, Prednisone, CB7630, Testosterone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Abiraterone plus leuprolide plus prednisone
Arm Type
Experimental
Arm Description
Abiraterone acetate tablets will be administered orally at a total dose of 1000 milligram (mg) per day up to Week 24. Leuprolide acetate will be administered at a dose of 22.5 mg (dose adjusted as per Investigator's discretion) as intramuscular injection (injection of a substance into a muscle) once every 12 weeks up to Week 24. Prednisone tablets will be administered orally as 5 mg once daily for 24 weeks.
Arm Title
Leuprolide then abiraterone plus leuprolide plus prednisone
Arm Type
Active Comparator
Arm Description
Leuprolide acetate will be administered at a dose of 22.5 mg as intramuscular injection once every 12 weeks up to Week 24. From Week 13 to 24, abiraterone acetate tablets will be administered orally at a total dose of 1000 mg per day with prednisone tablets administered orally as 5 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Abiraterone
Other Intervention Name(s)
CB7630
Intervention Description
Abiraterone acetate tablets will be administered orally at a total dose of 1000 milligram (mg) per day at least 1 hour before a meal or 2 hours after a meal for 24 weeks in Group 1 and from Week 13 to Week 24 for Group 2.
Intervention Type
Drug
Intervention Name(s)
Leuprolide
Intervention Description
Leuprolide acetate will be administered at a dose of 22.5 mg (dose adjusted as per Investigator's discretion) as intramuscular injection (injection of a substance into a muscle) once every 12 weeks in Group 1 and Group 2.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone tablets will be administered orally as 5 mg once daily for 24 weeks in Group 1 and from Week 13 to Week 24 for Group 2.
Primary Outcome Measure Information:
Title
Testosterone Concentration in Prostate Tissue
Description
Testosterone is a potent androgen (a hormone that promotes the development and maintenance of male characteristics) and major product secreted by cells in the testis and produced in the adrenal glands and by prostate cancers. Abiraterone acetate affects sources of testosterone in the body (ie, adrendal gland and prostate tumor). Testosterone concentration was measured in prostate tissues after exposure to study treatments at Week 12.
Time Frame
Week 12
Title
Dihydrotestosterone (DHT) Concentration in Prostate Tissue
Description
The DHT is a potent androgenic metabolite of testosterone and the concentration of DHT was measured in prostate tissues after exposure to study treatments at Week 12.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Testosterone and Dihydrotestosterone (DHT) Concentration in Prostate Tissue
Description
Testosterone is a potent androgen (a hormone that promotes the development and maintenance of male characteristics) and major product secreted by cells in the testis and produced in the adrenal glands and by prostate cancers. Dihydrotestosterone (DHT) is a potent androgenic metabolite of testosterone. Testosterone and DHT concentration was measured in prostate tissues after exposure to study treatments at Week 24.
Time Frame
Week 24
Title
Androstenedione and Dehydroepiandrosterone (DHEA) Concentrations in Prostate Tissue
Description
Androstenedione is a steroid (a group of polycyclic compounds closely related biochemically to terpenes, for example, cholesterol, numerous hormones), that is produced in the testis, ovary and the adrenal cortex, and depending on the tissue type, androstenedione can serve as a precursor to testosterone, estrone and estradiol. The DHEA is a major steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Androstenedione and DHEA concentration was measured in prostate tissues at Week 12 and 24.
Time Frame
Week 12 and 24
Title
Serum Levels of Androgens
Description
Serum concentrations of testosterone, DHT, androsterone, DHEA, DHEA-Sulfate, DHEA-Glucuronide and delta-4-androstenedione were measured at Weeks 12 and 24.
Time Frame
Week 12 and 24
Title
Percentage of Participants With Prostate-specific Antigen (PSA) Response
Description
The PSA response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criterion which is, percentage of participants with PSA less than or equal to 0.2 nanogram/milliliter at Weeks 12 and 24 after androgen deprivation.
Time Frame
Weeks 12 and 24
Title
Percentage of Participants With Pathologic Complete Response (CR)
Description
Complete response is defined as a disappearance of all target lesions and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criterion.
Time Frame
Week 24
Title
Number of Participants With Tumor Expression of Androgen Receptor (AR) Regulated Genes at Week 24
Description
Tumor expression of AR regulated genes determined by real-time polymerase chain reaction (RT PCR). PCR is an in vitro method for producing large amounts of specific deoxyribonucleic acid (DNA) or ribonucleic acid fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). RT PCR is a method used for detecting the amplified DNA products from the PCR as they accumulate instead of at the end of the reaction.
Time Frame
Week 24
Title
Correlation Between Molecular and Protein Expression With Intracellular Androgen Levels and Pathologic Response to Study Treatment
Description
Molecular and protein expression was correlated with intracellular androgen levels and pathologic response to study treatment.
Time Frame
Week 24
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the prostate
At least three core biopsies positive for prostate cancer (a minimum of 6 core biopsies must be obtained at baseline). A prostate biopsy within 6 months from Screening is allowed for entry requirements
At least one of the following features: prostate specific antigen (PSA) greater than (>) 10 nanogram per milliliter (ng/ml); PSA velocity >2 ng/ml per /year (defined as a rise in PSA of >2 ng/ml in the preceding 12 month period); Gleason score greater than or equal to (>=) 7 (4+3); Gleason score 6 if either PSA >=10 ng/ml or PSA velocity >=2 ng/ml/year
Serum testosterone >200 nanogram/deciliter
Participant and urologist must agree that participant is suitable for prostatectomy
Exclusion Criteria:
Serious or uncontrolled co-existent, non-malignant disease, including active and uncontrolled infection
Abnormal liver function consisting of any of the following: serum bilirubin >= 1.5 * upper limit of normal (ULN); aspartate aminotransferase or alanine aminotransferase >=2.5 * ULN
Uncontrolled hypertension within the Screening period (systolic blood pressure >= 160 millimeter of mercury [mmHg] or diastolic BP >= 95 mmHg)
Requirement for corticosteroids greater than the equivalent of 5 milligram of prednisone daily
Participants with active or symptomatic viral hepatitis or chronic liver disease or clinically significant heart disease or as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50 percent at Baseline or history of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug or history of pituitary or adrenal dysfunction
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Boston
State/Province
Massachusetts
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Wenatchee
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 2 Study to Evaluate Safety and Efficacy of Abiraterone Acetate in Male Participants With Prostate Cancer
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