A Safety and Efficacy Study of Abiraterone Acetate in Participants With Prostate Cancer Who Have Failed Hormone Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Abiraterone acetate
* Drug: Abiraterone acetate MTD
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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one hormonal therapy Prostate specific antigen (PSA) evidence for progressive prostate cancer Participants who were withdrawn from anti-androgen therapy less than 6 months prior to inclusion in the study require one PSA higher than the last pre-withdrawal PSA or 2 increases in PSA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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone acetate<br>Abiraterone acetate 250 mg up to a maximum of 2000 mg capsules will be given orally daily for 28-day treatment period to determine the MTD in Phase 1 of the study. Participants will receive MTD of abiraterone acetate for 12 cycles (28 day each) in Phase 2 of the study. Dexamethasone 0.5 mg will be given orally (If participants have disease progression) daily up to 12 cycles. | Drug: Abiraterone acetate<br>* Abiraterone 250 mg (1 capsule) up to 2000 mg (8 capsules) once daily, each dose will be tested in sequential order for 28 days to determine the MTD.<br>* Other names: CB7630;Drug: Abiraterone acetate MTD<br>* Abiraterone acetate MTD orally for 12 cycles (28 day each).<br>* Other names: CB7630;Drug: Dexamethasone<br>* Dexamethasone 0.5 mg orally will be given (If participants have disease progression) daily up to 12 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Confirmed Prostate Specific Antigen (PSA) Response at Week 12 | The PSA response was measured according to PSA working group (PSAWG) criteria. All participants achieving a fall in PSA of greater than 50 percent from baseline, which has been confirmed by a second measurement at least 4 weeks after initial documentation, fulfill criteria for confirmed PSA response. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Tumor Response | Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. | Baseline up to end of study (1160 days) | 
| Duration of Prostate Specific Antigen (PSA) Response | Duration of PSA response in participants on abiraterone acetate therapy was measured as the duration between PSA 50 percent decline date and PSA progression date as defined by the PSAWG criteria. | Baseline up to end of study (1160 days) | 
| Duration of Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | Number of participants with objective response based on assessment of confirmed CR or confirmed PR according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as greater than or equal to 30 percent decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. | Baseline up to end of study (1160 days) | 
| Time to Disease Progression | Disease progression was defined as greater than 25 percent increase in sum of longest diameter of target lesions compared to baseline. | Baseline up to end of study (1160 days) | 
| Overall Survival | Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact. | Baseline up to end of study (1160 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abiraterone acetate, CB7630, Prostatic neoplasms, Hormone refractory prostate cancer, Castration resistant prostate cancer, Castration refractory prostate cancer