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
概览
- 阶段
- 2 期
- 干预措施
- Abiraterone
- 疾病 / 适应症
- Prostate Cancer
- 发起方
- Janssen Research & Development, LLC
- 入组人数
- 58
- 主要终点
- Testosterone Concentration in Prostate Tissue
- 状态
- 已完成
- 最后更新
- 13年前
概览
简要总结
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).
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Abiraterone plus leuprolide plus prednisone
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.
干预措施: Abiraterone
Abiraterone plus leuprolide plus prednisone
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.
干预措施: Leuprolide
Abiraterone plus leuprolide plus prednisone
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.
干预措施: Prednisone
Leuprolide then abiraterone plus leuprolide plus prednisone
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.
干预措施: Abiraterone
Leuprolide then abiraterone plus leuprolide plus prednisone
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.
干预措施: Leuprolide
Leuprolide then abiraterone plus leuprolide plus prednisone
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.
干预措施: Prednisone
结局指标
主要结局
Testosterone Concentration in Prostate Tissue
时间窗: Week 12
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
时间窗: Week 12
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.
次要结局
- Testosterone and Dihydrotestosterone (DHT) Concentration in Prostate Tissue(Week 24)
- Androstenedione and Dehydroepiandrosterone (DHEA) Concentrations in Prostate Tissue(Week 12 and 24)
- Serum Levels of Androgens(Week 12 and 24)
- Percentage of Participants With Prostate-specific Antigen (PSA) Response(Weeks 12 and 24)
- Percentage of Participants With Pathologic Complete Response (CR)(Week 24)
- Number of Participants With Tumor Expression of Androgen Receptor (AR) Regulated Genes at Week 24(Week 24)
- Correlation Between Molecular and Protein Expression With Intracellular Androgen Levels and Pathologic Response to Study Treatment(Week 24)