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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00924469
• Other study ID #: CR016936
• Secondary ID: COU-AA-201
• Status: Completed
• Phase: Phase 2
• First received: June 17, 2009
• Last updated: March 6, 2013
• Start date: November 2009
• Est. completion date: March 2012

Study information

• Verified date: March 2013
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: March 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone
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.
• Leuprolide
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.
• Prednisone
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No