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

Phase 2
Completed
Conditions
Prostatic Neoplasms
Prostate Cancer
Interventions
Registration Number
NCT00485303
Lead Sponsor
Cougar Biotechnology, Inc.
Brief Summary

The purpose of this study is to evaluate the efficacy and safety of abiraterone acetate in participants with advanced prostate cancer (a disease in which cells in the prostate gland become abnormal and start to grow uncontrollably, forming tumors).

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 prostate cancer who have failed androgen deprivation and docetaxel-based chemotherapy. Abiraterone acetate oral tablet will be administered as a total dose of 1000 milligram (mg) orally (by mouth) once daily after an overnight fast and prednisone/prednisolone will be administered as 5 mg oral tablet twice daily. Participants will be enrolled and treated up to 12 cycles (or longer, if they have not progressed and continue to benefit from treatment). The study will consist of 3 parts: Screening (14 days), Open-label Treatment; and follow-up (up to 60 months). Participants will be evaluated primarily for prostate specific antigen response according to Prostate Specific Antigen Working Group (PSAWG) criteria. Participants' safety will be monitored throughout the study.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
58
Inclusion Criteria
  • Histologically or cytologically confirmed adenocarcinoma (malignant epithelial tumor with a glandular organization)of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum), but not with neuroendocrine (specialized neurons that produce hormones, such as neuropeptides or biogenic amines) differentiation or of small cell histology
  • Prior chemotherapy (treatment of disease, usually cancer, by chemical agents) for prostate cancer with regimen(s) containing docetaxel
  • Documented prostate specific antigen (PSA) progression according to Prostate Specific Antigen Working Group (PSAWG) eligibility criteria with a PSA more than (>) 5 nanogram per milliliter (ng/mL) or objective progression by Response Evaluation Criteria in Solid Tumors (RESIST) criteria
  • Ongoing androgen deprivation with serum testosterone less than (<) 50 nanogram per deciliter (ng/dL)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of less than equal to (<=) 2 (Karnofsky Performance Status >= 50 percent)
Exclusion Criteria
  • 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
  • Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection
  • Uncontrolled hypertension (high blood pressure)
  • Hemoglobin <=9.0 gram per deciliter (g/dL) without growth factor or transfusion support
  • Abnormal liver (large organ that helps in many body functions, including digestion, metabolism, and storage of substances) function

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AbirateronePrednisoneAbiraterone acetate 1000 milligram (mg) (4 oral tablets of 250 mg each) will be administered once daily along with 5 mg oral prednisolone tablet administered twice daily for 28-days dosing cycle and will be continued until disease progression or unacceptable toxicity.
AbirateroneAbiraterone acetateAbiraterone acetate 1000 milligram (mg) (4 oral tablets of 250 mg each) will be administered once daily along with 5 mg oral prednisolone tablet administered twice daily for 28-days dosing cycle and will be continued until disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Prostate Specific Antigen (PSA) ResponseDay 1 of each cycle (of 28 days each) up to Cycle 12

The PSA response was evaluated according to Prostate-Specific Antigen Working Group (PSAWG) criterion, which is, greater than or equal to 50 percent decrease in PSA from Baseline during the study, which would be subsequently confirmed by a measurement that is at least 4 or more weeks after initial documentation of PSA response.

Secondary Outcome Measures
NameTimeMethod
Prostate-Specific Antigen Based Progression-free Survival (PSA-PFS)Baseline and Day 1 of each cycle until first documented disease progression or up to 60 months

The PSA-PFS is defined as time to first PSA failure (that is, two consecutive increases in PSA of 50 percent and greater than or equal to 5 nanogram per milliliter, as per Prostate-Specific Antigen Working Group \[PSAWG\] criterion) or death or the start of secondary anti-tumor therapy, whichever occurs first. If a PSA progression or death does not occur, subject will be censored at the last PSA evaluation.

Radiographic Progression Free Survival (PFS)Baseline, Day 1 of Cycle 4, 7 and 10, and thereafter every third cycle until first documented disease progression or up to 60 months

The RAD-PFS is defined as the time from randomization to the earliest objective evidence of radiographic progression or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Overall Survival (OS)Every 3 months until death or up to 60 months

Overall survival is defined as the interval from the date of the first dose of abiraterone acetate to the date of death.

Percentage of Participants With Objective Radiographic ResponseBaseline, Day 1 of Cycle 4, 7 and 10, and thereafter every third cycle until first documented disease progression or up to 60 months

Percentage of participants with radiographic objective response is defined as the percentage of participants with complete response (CR) or partial response (PR) as best overall response based on reconciled radiographic disease assessment according to RECIST Version 1.0. The CR is disappearance of all lesions. The PR is at least 30 percent decrease in sum of the longest diameter of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Time to PSA ProgressionDay 8 of Cycle 1, thereafter Day 1 of each cycle up to end of study (60 months)

The time interval from first dose of abiraterone acetate to the date of PSA progression as defined by the Prostate-Specific Antigen Working Group (PSAWG) criteria. If a PSA progression does not occur, subject will be censored at the last PSA evaluation.

Time to Radiographic ProgressionBaseline, Day 1 of Cycle 4, 7 and 10, and thereafter every third cycle until first documented disease progression or up to 60 months

Time to radiographic progression is defined as the time from first dose until the first radiographic progression date that was confirmed.

Shift From Baseline in Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status ScoreBaseline and Day 1 of each cycle until first documented disease progression or up to 60 months

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 percent of waking hours, 3=capable of limited self-care, confined to bed or chair \>50 percent of waking hours, 4=completely disabled, not capable of any self-care, totally confined to bed or chair and 5=dead.

Percentage of Participants With Clinical BenefitBaseline, Day 1 of Cycle 4, 7 and 10, and thereafter every third cycle until first documented disease progression or up to 60 months

Clinical benefit was defined as an observation of at least 1 of the following: PSA response by PSAWG criteria; radiographic response by RECIST criteria; stable disease by RECIST criteria lasting 6 months; or improvement by at least 1 unit in ECOG performance status.

Trial Locations

Locations (8)

UCSF Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

UCLA

🇺🇸

Los Angeles, California, United States

Beth Israel Hospital

🇺🇸

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Royal Marsden Hospital

🇬🇧

Sutton, United Kingdom

Masachussetts General Hospital Cancer Center

🇺🇸

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

John Hopkins

🇺🇸

Baltimore, Maryland, United States

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