Clinical trial NCT00473512: A Safety and Efficacy Study of Abiraterone Acetate in Participants With Prostate Cancer Who Have Failed Hormone Therapy
Official title: A Phase I/II Open Label Study of the 17α-Hydroxylase/ C17,20 Lyase Inhibitor, Abiraterone Acetate in Patients With Prostate Cancer Who Have Failed Hormone Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms
Keywords: Abiraterone acetate
CB7630
Prostatic neoplasms
Hormone refractory prostate cancer
Castration resistant prostate cancer
Castration refractory prostate cancer
Lead sponsor: Cougar Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2007-05-15
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose and evaluate the safety, tolerability, and activity at the recommended dose (maximum tolerated dose \[MTD\]) of abiraterone acetate (also known as CB7630) in participants with hormone refractory prostate (gland that makes fluid that aids movement of sperm) cancer (HRPC).

Detailed description: This is an open-label (all people know the identity of the intervention) study to evaluate the safety, tolerability, and recommended dose of abiraterone acetate taken orally (by mouth), once daily in participants with HRPC. The study will consist of a dose escalation stage (Phase 1) that will be conducted to determine the MTD of abiraterone and an activity evaluation stage (Phase 2) to evaluate the activity of abiraterone in participants with HRPC. Escalated doses of abiraterone (starting at 250 milligram \[mg\] up to a maximum of 2000 mg) will be given for 28-day treatment periods to determine the MTD. Participants will be given MTD of abiraterone for up to 12 cycles (28 day each) in Phase 2 of the study. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically (pertaining to the disease status of body tissues or cells) documented adenocarcinoma of the prostate, clinically refractory (not responding to treatment) or resistant to hormone therapy, as documented by progression following at least one hormonal therapy
* Prostate specific antigen (PSA) evidence for progressive prostate cancer
* Participants who were withdrawn from anti-androgen therapy less than 6 months prior to inclusion in the study require one PSA higher than the last pre-withdrawal PSA or 2 increases in PSA documented after the post-withdrawal nadir(value) greater than or equal to 4 weeks from treatment withdrawal if treated with flutamide and greater than or equal to 6 weeks if treated with bicalutamide or nilutamide
* Eastern Cooperative Oncology Group (ECOG) performance status score equal to 0 or 1
* Life expectancy of greater than or equal to12 week

Exclusion Criteria:

* Participants with central nervous system (the brain and spinal cord) disease and/or brain metastases
* No currently active second malignancy (cancer or other progressively enlarging and spreading tumor) other than non-melanoma skin cancer
* Myocardial infarction within the 6 months prior to start of study
* No active or uncontrolled autoimmune disease (disorder in which a person's immune system attacks parts of his or her own body) that may require corticosteroid therapy during protocol treatment
* Major surgery or significant traumatic injury within 4 weeks of start of study

Primary outcomes:
measure: Number of Participants With Confirmed Prostate Specific Antigen (PSA) Response at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Number of Participants With Objective Tumor Response
timeFrame: Baseline up to end of study (1160 days)
measure: Duration of Prostate Specific Antigen (PSA) Response
timeFrame: Baseline up to end of study (1160 days)
measure: Duration of Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Baseline up to end of study (1160 days)
measure: Time to Disease Progression
timeFrame: Baseline up to end of study (1160 days)
measure: Overall Survival
timeFrame: Baseline up to end of study (1160 days)
Other outcomes:
measure: Serum Blood Levels of Testosterone
timeFrame: Baseline, Cycle 2 (within 3 days prior to Day 29)
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after the last dose of study medication
measure: Serum Blood Levels of Testosterone Precursors
timeFrame: Baseline, Cycle 2 (within 3 days prior to Day 29)
measure: Time to Prostate Cancer Pain Progression
timeFrame: Baseline up to 12 cycles
measure: Number of Participants With Change From Baseline in Biochemical Bone Markers
timeFrame: Baseline, Cycle 2, 4, 8, 12
measure: Mean Plasma Concentration of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
measure: Maximum Observed Plasma Concentration (Cmax) of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
measure: Plasma Decay Half-Life (t1/2) of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
measure: Time to Last Quantifiable Plasma Concentration (Tlast) of Abiraterone
timeFrame: Pre-dose on Day 1, 8 and 15 of Cycle 1, Day 1 of Cycle 2, Day 1 of Cycle 3; 1, 2, 4, 6, 8, 24, 48 and 72 hours after first dose was given
Locations:
city: Sutton
country: United Kingdom
Study officials:
affiliation: Cougar Biotechnology, Inc.
name: Cougar Biotechnology Clinical Trial
role: STUDY_DIRECTOR
References: