A Phase 2 Study to Evaluate Safety and Efficacy of Abiraterone Acetate in Male Participants With Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone
* Drug: Leuprolide
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone plus leuprolide plus prednisone<br>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. | Drug: Abiraterone<br>* 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.<br>* Other names: CB7630;Drug: Leuprolide<br>* 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.<br>Drug: Prednisone<br>* 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.<br>|
| Active Comparator: Leuprolide then abiraterone plus leuprolide plus prednisone<br>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. | Drug: Abiraterone<br>* 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.<br>* Other names: CB7630;Drug: Leuprolide<br>* 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.<br>Drug: Prednisone<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | Week 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. | Weeks 12 and 24 | 
| 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. | Week 24 | 
| 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. | Week 24 | 
| 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. | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Abiraterone acetate, Leuprolide acetate, Prednisone, CB7630, Testosterone