An Safety and Efficacy Study of Abiraterone Acetate in Participants With Advanced Prostate Cancer Who Failed Androgen Deprivation and Docetaxel-Based Chemotherapy

• ClinicalTrials.gov Identifier: NCT00474383
• Recruitment Status: Completed
• First Posted: May 16, 2007
• Results First Posted: August 15, 2013
• Last Update Posted: May 12, 2014
• Sponsor: Cougar Biotechnology, Inc.
• Information provided by (Responsible Party): Cougar Biotechnology, Inc.

Tracking Information

• First Submitted Date: May 14, 2007
• First Posted Date: May 16, 2007
• Results First Submitted Date: May 13, 2013
• Results First Posted Date: August 15, 2013
• Last Update Posted Date: May 12, 2014
• Study Start Date: November 2006
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2013)

Percentage of Participants With Confirmed Prostate Specific Antigen (PSA) Response at Week 12 [ Time Frame: Baseline, Week 12 ]

The PSA response was evaluated according to Prostate-Specific Antigen Working Group (PSAWG) criteria, which was, greater than or equal to 50 percent decrease in PSA from Baseline and confirmed by subsequent measurement at least 4 weeks later.

• Original Primary Outcome Measures (submitted: May 14, 2007): Anti-tumor effects [ Time Frame: Disease progression ]

Current Secondary Outcome Measures (submitted: May 23, 2013)

• Percentage of Participants With Confirmed Prostate Specific Antigen (PSA) Response [ Time Frame: Baseline up to Week 12 ]
  The PSA response was evaluated according to Prostate-Specific Antigen Working Group (PSAWG) criteria, which was, greater than or equal to 50 percent decrease in PSA from Baseline and confirmed by subsequent measurement at least 4 weeks later.
• Percentage of Participants With Confirmed Objective Tumor Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline until first documented disease progression or end of study visit (Week 148; assessed on Day 1 of Cycle 4, 7, 10, and thereafter Day 1 of each cycle) ]
  The objective tumor response was defined as the percentage of participants achieving a complete (CR) or partial response (PR) on tumor response assessed as per RECIST. The CR was disappearance of all lesions. The PR was at least a 30 percent decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Baseline sum LD.
• Time to PSA Progression [ Time Frame: Baseline until first documented disease progression or up to end of study (Week 148; assessed on Days 1, 8 of Cycle 1, thereafter Day 1 of each Cycle) ]
  The time to PSA progression was the interval from the date of the first dose of abiraterone acetate to the date of PSA progression as defined by the PSAWG criteria. PSA progression was defined as a 50 percent increase over the nadir PSA value, increase in the PSA level by at least 5 nanogram per milliliter (ng/mL), and confirmed by second consecutive measurement.
• Duration of PSA Response [ Time Frame: Baseline until first documented disease progression or up to end of study (Week 148; assessed on Days 1, 8 of Cycle 1, thereafter Day 1 of each Cycle) ]
  Duration of PSA response was the time between the date of first PSA response (greater than or equal to 50 percent decline from Baseline) and the date of PSA progression as defined by the PSAWG. PSA progression was defined as a 50 percent increase over the nadir PSA value, increase in the PSA level by at least 5 nanogram per milliliter (ng/mL), and confirmed by second consecutive measurement.
• Progression Free Survival Time [ Time Frame: Baseline until first documented disease progression or death or up to end of study (Week 148; assessed on Day 1 of each cycle) ]
  Progression Free Survival was defined as the interval from the date of the first dose of abiraterone acetate to the date of death or date of progressive disease (PD) as assessed by RECIST criteria. PD was at least 20 percent increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
• Overall Survival [ Time Frame: Baseline until death, or end of study (Week 148) ]
  Overall survival was defined as the interval from the date of the first dose of abiraterone acetate to the date of death.
• Shift From Baseline in Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score at Post-dose (Week 148) [ Time Frame: Baseline until first documented disease progression or up to end of study (Week 148; assessed on Day 1 of each cycle) ]
  The ECOG performance status score ranges from 0 to 5 where 0=fully active, perform all pre-disease activities without restriction; 1=restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature; 2=ambulatory, capable of self-care, unable to carry out any work activities, up and about more than (>) 50 percentage of waking hours; 3=capable of limited self-care, confined to bed or chair >50 percentage of waking hours; 4=completely disabled, not capable of any self-care, totally confined to bed or chair; and 5=dead.

• Original Secondary Outcome Measures (submitted: May 14, 2007): Safety [ Time Frame: Duration of Study ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Safety and Efficacy Study of Abiraterone Acetate in Participants With Advanced Prostate Cancer Who Failed Androgen Deprivation and Docetaxel-Based Chemotherapy
• Official Title: A Phase II Open Label Study of CB7630 (Abiraterone Acetate) in Patients With Advanced Prostate Cancer Who Have Failed Androgen Deprivation and Docetaxel-Based Chemotherapy
• Brief Summary: The purpose of this study is to assess the anti-tumor activities and safety of abiraterone acetate in participants with prostate cancer (a disease in which cells in the prostate gland [a gland in the male reproductive system found below the bladder and in front of the rectum] become abnormal and start to grow uncontrollably, forming tumors) who have failed taxane (docetaxel)-based chemotherapy.
• Detailed Description: This is an open-label (all people know the identity of the intervention), single arm, multicenter (when more than one hospital or medical school team work on a medical research study) study to evaluate the anti-tumor activities and safety of abiraterone acetate in participants with cancer who have failed taxane (docetaxel)-based chemotherapy. Abiraterone acetate 1000 milligram (mg) tablet or capsule will be administered orally (by mouth), once daily after an overnight fast until disease progression, lack of disease response after six 28-day cycles of treatment, or when unacceptable toxicity is encountered. Participants will be treated for up to 12 cycles. All participants will receive a concurrent low-dose glucocorticoid (such as prednisone 5 mg tablet twice daily/prednisolone 0.5 mg tablet once daily). Treatment will be continued in responding participants until death, or disease progression, or end of the study (which is Week 148). Efficacy will primarily be assessed through prostate specific antigen response according to Prostate Specific Antigen Working Group (PSAWG) criteria. Participants' safety will be monitored throughout the study. Participants who have completed 12 cycles of abiraterone acetate treatment, and continue to receive clinical benefit from such treatment, will be eligible to enter the extension study. Participants who enter the extension study will continue taking abiraterone acetate at the dose they were receiving at the end of the main study together with low-dose glucocorticoid. Efficacy and safety will be monitored throughout the extension study. Study treatment will end when the patient dies, is lost to follow-up, withdraws informed consent, experiences sustained side-effects, has disease progression, or the sponsor discontinues the extension study. After the end of study visit is completed for the extension study, participants will be followed every 12 weeks for survival for up to 3 years following entry into the extension study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Neoplasms

Intervention

• Drug: Abiraterone acetate
  Abiraterone acetate 1000 milligram (mg) capsule or tablet will be administered orally, once daily continuously in 28-day cycle up to disease progression, death, or end of study.
• Drug: Glucocorticoid
  Prednisone/prednisolone 5 mg tablet orally twice daily/dexamethasone 0.5 mg tablet orally once daily continuously in 28-day cycle up to disease progression, death, or end of study.

Study Arms

Experimental: Abiraterone acetate

Abiraterone acetate 1000 milligram (mg) tablet or capsule will be administered orally, once daily continuously in 28-day cycle up to disease progression, death, or end of study, along with prednisone/prednisolone 5 mg tablet orally twice daily or dexamethasone 0.5 mg tablet orally once daily.

Interventions:

• Drug: Abiraterone acetate
• Drug: Glucocorticoid

• Publications *: Danila DC, Anand A, Sung CC, Heller G, Leversha MA, Cao L, Lilja H, Molina A, Sawyers CL, Fleisher M, Scher HI. TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Eur Urol. 2011 Nov;60(5):897-904. doi: 10.1016/j.eururo.2011.07.011. Epub 2011 Jul 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 8, 2012): 47
• Original Estimated Enrollment (submitted: May 14, 2007): 33
• Actual Study Completion Date: August 2011
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma (cancer that begins in cells that line certain internal organs and that have secretory properties) of the prostate, but not with neuroendocrine differentiation or of small cell histology
• Before chemotherapy for prostate cancer with regimen(s) containing paclitaxel or docetaxel
• Documented prostate-specific antigen (PSA) progression according to PSA working group eligibility criteria with a PSA greater than 5 nanogram per milliliter (ng/mL)
• Ongoing androgen deprivation with serum testosterone level of less than 50 nanogram per deciliter (ng/dL)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2 (Karnofsky Performance Status greater than or equal 50 percentage)

Exclusion Criteria:

• Active or uncontrolled autoimmune disease that may require corticosteroid therapy
• Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
• Uncontrolled hypertension
• Clinically significant heart disease as evidenced by a myocardial infarction in the past 12 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease (participants with a history of atherosclerotic vascular disease requiring coronary or peripheral artery bypass surgery may be enrolled provided the surgery occurred at least 2 years before to enrollment and after consultation with a cardiologist to insure that the disease is stable)
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study medication

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT00474383
• Other Study ID Numbers: CR016915; COU-AA-003; COU-AA-003EXT
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Cougar Biotechnology, Inc.
• Study Sponsor: Cougar Biotechnology, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Cougar Biotechnology, Inc. Clinical Trial; Cougar Biotechnology, Inc.

• PRS Account: Cougar Biotechnology, Inc.
• Verification Date: April 2014