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Abiraterone Acetate Dose-Escalation Study in Hormone Refractory Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00473746
First received: May 11, 2007
Last updated: March 22, 2013
Last verified: March 2013
History of Changes
  Purpose

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics, and anti‑tumor activities of abiraterone acetate (also referred to as CB7630) in patients with hormone refractory prostate cancer (HRPC).


Condition Intervention Phase
Prostate Neoplasms
 Drug: Abiraterone acetate
Drug: prednisone/prednisolone or 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: Phase I/II Open Label Dose Escalation Study of the 17α-Hydroxylase/ C17,20-Lyase Inhibitor, Abiraterone Acetate in Hormone Refractory Prostate Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Phase 1: maximum tolerated dose of CB7630 [ Time Frame: Up to Cycle 12, Day 28 ] [ Designated as safety issue: Yes ]
  • Phase 2: number of patients achieving a >=50% prostate specific antigen (PSA) decline [ Time Frame: Up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Number of patients requiring corticosteroid supplementation [ Time Frame: Phase 1, up to Cycle 12, Day 28 ] [ Designated as safety issue: Yes ]
  • Mean plasma concentrations of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Maximum plasma concentrations of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Time to reach the maximum plasma concentration of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-time curve from time 0 to the last quantifiable concentration of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-time curve from time 0 to infinite time of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Elimination half-life of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Objective tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Phase 1, at tumor progression up to Cycle 12, Day 28 or disease progression ] [ Designated as safety issue: No ]
  • Objective tumor response by Prostate Specific Antigen (PSA) Working Group Criteria [ Time Frame: Phase 1, at tumor progression up to Cycle 12, Day 28 or disease progression ] [ Designated as safety issue: No ]
  • Radiographic progression free survival [ Time Frame: Phase 2, up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]
  • PSA progression free survival [ Time Frame: Phase 2, up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]
  • Radiographic objective response rate [ Time Frame: Phase 2, up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Phase 2, up to Month 60 ] [ Designated as safety issue: No ]
  • Duration of PSA decline >=50% [ Time Frame: Phase 2, up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]
  • Number of participants with change in Eastern Cooperative Oncology Group (ECOG) performance status score [ Time Frame: Phase 2, up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]
  • Time to tumor progression [ Time Frame: Phase 2, at tumor progression up to 12 weeks from start of treatment ] [ Designated as safety issue: No ]
  • Patients with change in adrenal steroidogenesis assessment [ Time Frame: Baseline and up to end of study visit (up to Month 60) ] [ Designated as safety issue: No ]
  • Terminal half life of abiraterone [ Time Frame: Phase 1 pre-dose and 1, 2, 4, 6, 8, 12, 24, and 48 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: June 2006
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I Dose Escalation Drug: Abiraterone acetate
The first cohort was a abiraterone acetate 250 mg/day orally (by mouth), once daily for 28-day treatment periods , if no dose limiting toxicity (DLT) was documented at this dose, the dose will be escalated to next dose levels 500, 750, and 1000 mg/day. The dose escalation will continue to a maximum of 1000mg/day until Maximum Tolerated Dose (MTD) and a recommended Phase II dose was established.
Experimental: Phase II Dose Treatment Drug: Abiraterone acetate
Abiraterone acetate 1000 mg daily under fasted conditions upto 10 cycles of therapy.
Drug: prednisone/prednisolone or dexamethasone
prednisone/prednisolone (5 mg twice daily) or dexamethasone (0.5 mg once daily) concurrent with abiraterone acetate

Detailed Description:

This is an open-label (identity of assigned study drug will be known) study to evaluate the safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of what a drug does to the body), and anti-tumor activities of abiraterone acetate (also known as CB7630) in patients with HRPC. The study will be conducted in 2 phases (Phase 1 and Phase 2). In the first part of the study (Phase 1), the maximum tolerated dose (MTD) of abiraterone acetate will be determined for use in the second part of the study (Phase 2) where the number of patients who achieve at least a 50% decrease in prostate specific antigen (PSA) during treatment with abiraterone acetate will be assessed (MTD from Phase 1). Abiraterone acetate will be taken orally (by mouth) in fed and fasted patients once daily. Doses of abiraterone acetate (starting at 250 mg up to a maximum of 2000 mg) will be taken for 28-day treatment periods to determine the MTD. Patients will take MTD of abiraterone acetate for up to twelve 28 day cycles (12 months; patients will be given the option of staying on abiraterone acetate treatment if they are deriving benefit). In Phase 2, prednisone or dexamethasone will be administered concurrently with abiraterone acetate. Serial pharmacokinetic and pharmacodynamic samples will be collected and 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:

Phase 1

  • Histologically confirmed adenocarcinoma of the prostate
  • No prior therapy with chemotherapy for prostate cancer
  • Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy
  • Testosterone <50 ng/dL
  • Progressive disease after androgen deprivation
  • The presence of objective metastatic disease is NOT required for study eligibility
  • Demonstrate disease progression after antiandrogen withdrawal
  • Eastern Cooperative Oncology Group (ECOG) performance status score = 0-1
  • Laboratory values within protocol-defined parameters
  • Systolic blood pressure <160 mmHg and diastolic blood pressure <110mmHg documented on at least 3 different days
  • Baseline adrenocorticotropic hormone (ACTH) stimulation test demonstrating a peak cortisol >18 µg/dL
  • Agrees to protocol-defined use of effective contraception
  • Life expectancy of >=12 weeks

Phase 2

  • Same as Phase 1 criteria with addition of following criteria
  • Neoadjuvant or adjuvant chemotherapy is only allowed if the last dose is >1 year from Cycle 1 Day 1
  • Target or non-target abnormalities must be present either on screening bone scan, computed tomography or magnetic resonance imaging
  • No prior treatment with ketoconazole for the management of androgen independent prostate cancer

Exclusion Criteria:

Phase 1

  • Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease prostate specific antigen (PSA) levels (eg, saw palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug
  • Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug
  • Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: conventional multivitamin supplements, selenium, lycopene, soy supplements
  • Prior radiation therapy completed <4 weeks prior to enrollment
  • Prior chemotherapy for hormone refractory prostate cancer
  • Any currently active second malignancy, other than non-melanoma skin cancer
  • Systolic blood pressure >=160 mmHg or diastolic blood pressure >=110 mmHg measured on at least 2 occasions
  • NYHA Class III or IV congestive heart failure
  • Myocardial infarction within the 6 months prior to the first dose of study drug
  • Serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled
  • Active psychiatric illnesses/social situations that would limit compliance with protocol requirements
  • Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study

Phase 2

  • Same as phase 1 with the following addition
  • Abnormal electrocardiogram, including any finding which would interfere with assessment of intervals (patients with long QT syndrome, bundle branch blocks or hemiblocks are prohibited)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00473746

Locations
United States, California
San Francisco, California, United States
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Massachusetts
Boston, Massachusetts, United States
Massachussetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Texas
Houston, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
NATIONAL CANCER INSTITUTE  This link exits the ClinicalTrials.gov site
PROSTATE CANCER  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00473746     History of Changes
Other Study ID Numbers: CR016969, COU-AA-002
Study First Received: May 11, 2007
Last Updated: March 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Prostate neoplasms
Hormone refractory prostate cancer
Abiraterone acetate
CB7630

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Dexamethasone acetate
Methylprednisolone acetate
Prednisolone acetate
Dexamethasone
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisone
 Dexamethasone 21-phosphate
Prednisolone hemisuccinate
Prednisolone phosphate
Hormones
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on May 19, 2013