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

Prostatic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00473512
• Other study ID #: CR016909
• Secondary ID: COU-AA-001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 11, 2007
• Last updated: February 27, 2014
• Start date: November 2005
• Est. completion date: November 2008

Study information

• Verified date: February 2014
• Source: Cougar Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone acetate
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.
• Abiraterone acetate MTD
Abiraterone acetate MTD orally for 12 cycles (28 day each).
• Dexamethasone
Dexamethasone 0.5 mg orally will be given (If participants have disease progression) daily up to 12 cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cougar Biotechnology, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Blood Levels of Testosterone	Concentration of testosterone in blood was measured in nanogram per deciliter (ng/dL).	Baseline, Cycle 2 (within 3 days prior to Day 29)	No
Other	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to 30 days after the last dose of study medication	Yes
Other	Serum Blood Levels of Testosterone Precursors	Concentration of Cortisol, Aldosterone, Corticosterone, 11-Deoxycortisol, Deoxycorticosterone and Dehydroepiandrostenedione Sulphate (DHEA-S) in blood was measured in nanogram per deciliter (ng/dL).	Baseline, Cycle 2 (within 3 days prior to Day 29)	No
Other	Time to Prostate Cancer Pain Progression	The time from start of study treatment to the development/worsening of pain due to prostate cancer requiring one or more of the following treatments: 1- Opioid therapy (therapy with morphine like medicines for 10 out of 14 consecutive days); 2- Glucocorticoid therapy; 3- Initiation of >= 5 mg of prednisolone for 10 out of 14 consecutive days; 4- Radionuclide therapy; 5- Radiation therapy (x-ray or cobalt treatment); 6- Chemotherapy (treatment of disease by chemical agents). Participants who do not experience prostate cancer pain were censored on their last day on study. Time to prostate cancer pain progression was measured by Kaplan-Meier method.	Baseline up to 12 cycles	No
Other	Number of Participants With Change From Baseline in Biochemical Bone Markers		Baseline, Cycle 2, 4, 8, 12	No
Other	Mean Plasma Concentration of Abiraterone		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	No
Other	Maximum Observed Plasma Concentration (Cmax) of Abiraterone	The Cmax is defined as maximum observed analyte concentration.	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	No
Other	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone	The Tmax is defined as actual sampling time to reach maximum observed plasma concentration. The analyte concentration associated with Tmax is referred to as Cmax.	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	No
Other	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Abiraterone	Area under the plasma concentration time-curve from time zero to the last quantifiable concentration (AUClast).	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	No
Other	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] of Abiraterone	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	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	No
Other	Plasma Decay Half-Life (t1/2) of Abiraterone	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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	No
Other	Time to Last Quantifiable Plasma Concentration (Tlast) of Abiraterone	The actual sampling time of last measurable (non-below the limit of quantification [BQL]) analyte concentration. The analyte concentration associated with Tlast is referred to as Clast.	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	No
Primary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No

External Links

•   NATIONAL CANCER INSTITUTE
•   PROSTATE CANCER