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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cougar Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00473512
First received: May 11, 2007
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Prostatic Neoplasms
Drug: Abiraterone acetate
Drug: Abiraterone acetate MTD
Drug: Dexamethasone
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Cougar Biotechnology, Inc.:

Primary Outcome Measures:
  • Number of Participants With Confirmed Prostate Specific Antigen (PSA) Response at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Objective Tumor Response [ Time Frame: Baseline up to end of study (1160 days) ] [ Designated as safety issue: No ]
    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.

  • Duration of Prostate Specific Antigen (PSA) Response [ Time Frame: Baseline up to end of study (1160 days) ] [ Designated as safety issue: No ]
    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.

  • Duration of Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline up to end of study (1160 days) ] [ Designated as safety issue: No ]
    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.

  • Time to Disease Progression [ Time Frame: Baseline up to end of study (1160 days) ] [ Designated as safety issue: No ]
    Disease progression was defined as greater than 25 percent increase in sum of longest diameter of target lesions compared to baseline.

  • Overall Survival [ Time Frame: Baseline up to end of study (1160 days) ] [ Designated as safety issue: No ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.


Other Outcome Measures:
  • Serum Blood Levels of Testosterone [ Time Frame: Baseline, Cycle 2 (within 3 days prior to Day 29) ] [ Designated as safety issue: No ]
    Concentration of testosterone in blood was measured in nanogram per deciliter (ng/dL).

  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
    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.

  • Serum Blood Levels of Testosterone Precursors [ Time Frame: Baseline, Cycle 2 (within 3 days prior to Day 29) ] [ Designated as safety issue: No ]
    Concentration of Cortisol, Aldosterone, Corticosterone, 11-Deoxycortisol, Deoxycorticosterone and Dehydroepiandrostenedione Sulphate (DHEA-S) in blood was measured in nanogram per deciliter (ng/dL).

  • Time to Prostate Cancer Pain Progression [ Time Frame: Baseline up to 12 cycles ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Change From Baseline in Biochemical Bone Markers [ Time Frame: Baseline, Cycle 2, 4, 8, 12 ] [ Designated as safety issue: No ]
  • Mean Plasma Concentration of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Maximum Observed Plasma Concentration (Cmax) of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The Cmax is defined as maximum observed analyte concentration.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from time zero to the last quantifiable concentration (AUClast).

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

  • Plasma Decay Half-Life (t1/2) of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Time to Last Quantifiable Plasma Concentration (Tlast) of Abiraterone [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 54
Study Start Date: November 2005
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abiraterone acetate
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
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.
Other Name: CB7630
Drug: Abiraterone acetate MTD
Abiraterone acetate MTD orally for 12 cycles (28 day each).
Other Name: CB7630
Drug: Dexamethasone
Dexamethasone 0.5 mg orally will be given (If participants have disease progression) daily up to 12 cycles.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00473512

Locations
United Kingdom
Sutton, United Kingdom
Sponsors and Collaborators
Cougar Biotechnology, Inc.
Investigators
Study Director: Cougar Biotechnology Clinical Trial Cougar Biotechnology, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Cougar Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00473512     History of Changes
Other Study ID Numbers: CR016909, COU-AA-001
Study First Received: May 11, 2007
Results First Received: June 7, 2013
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cougar Biotechnology, Inc.:
Abiraterone acetate
CB7630
Prostatic neoplasms
Hormone refractory prostate cancer
Castration resistant prostate cancer
Castration refractory prostate cancer

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Hormones
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014