An Observational Study of Continuous Oral Dosing of Abiraterone Acetate in Castration-Resistant Prostate Cancer Patients Evaluating Androgens and Steroid Metabolites in Bone Marrow Plasma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00544440
First received: October 15, 2007
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to investigate the effect of abiraterone acetate on levels of androgens and steroid metabolites in bone marrow plasma of patients with metastatic castration-resistant prostate cancer (CRPC).


Condition Intervention Phase
Prostate Neoplasms
Drug: Abiraterone acetate
Drug: Prednisone
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: An Observational Study of Continuous Oral Dosing of an Irreversible CYP17 Inhibitor, Abiraterone Acetate (CB7630), in Castration-Resistant Prostate Cancer Patients Evaluating Androgens and Steroid Metabolites in Bone Marrow Plasma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants With Detectable Bone Marrow Testosterone Level (>1 Picograms/Mililiter) [ Time Frame: Baseline (predose Week 1 Day 1) and Week 8 ] [ Designated as safety issue: No ]
  • Number of Participants With Detectable Bone Marrow Dihydrotestosterone (DHT) Level (>9 Picograms/Mililiter) [ Time Frame: Baseline (predose Week 1 Day 1) and Week 8 ] [ Designated as safety issue: No ]
  • Difference in Bone Marrow Testosterone Levels Between Participants With and Without Serum Prostate Specific Antigen Decline [ Time Frame: Week 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants With Change in Markers of Bone Metabolism [ Time Frame: Week 8 ] [ Designated as safety issue: No ]

Enrollment: 57
Study Start Date: October 2007
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abiraterone acetate plus prednisone
Patients will be treated orally with abiraterone acetate 1000 mg daily and prednisone 5 mg twice a day until clinical disease progression.
Drug: Abiraterone acetate
Abiraterone 1000 mg (4 x 250 mg tablets) taken orally once daily
Drug: Prednisone
Prednisone 5 mg tablet taken orally twice daily

Detailed Description:

This is a single-center, open-label (identity of assigned study drug will be known) study investigating the effect of abiraterone acetate on levels of testosterone and dihydrotestosterone (DHT) in bone marrow plasma of patients with metastatic CRPC and evaluating the difference in bone marrow androgen levels between patients with and without serum prostate specific antigen (PSA) decline. Approximately 60 medically or surgically castrated male patients with metastatic CRPC will be enrolled. The study will consist of screening, treatment, and follow-up periods. Patients will be treated orally (by mouth) with abiraterone acetate 1000 mg daily and prednisone 5 mg twice a day until clinical disease progression. Follow-up will continue until the patient dies, is lost to follow-up or withdraws informed consent. Bone marrow aspirates will be collected at Week 1 (predose), Week 9, and the final study visit. 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 proven adenocarcinoma of the prostate
  • Eastern Cooperative Oncology Group (ECOG) performance status <=2 (Karnofsky Performance Status >=50%)
  • Serum testosterone levels <50ng/ml
  • Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy (patients, who have not had an orchiectomy, must be maintained on effective LHRH analogue therapy for the duration of the study)
  • Progression of disease despite androgen ablation (either documented osseous or soft tissue metastatic disease progression or by prostate specific antigen [PSA] criteria progression)
  • Progressive disease is defined by PSA evidence (PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart)
  • Presence of metastatic bone disease
  • Discontinue diethylstilbestrol or steroids treatment for >=4 weeks and for antiandrogens >6 weeks
  • Antiandrogen withdrawal: patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen (disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression)
  • For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation
  • For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation
  • Adequate adrenal function
  • Laboratory values within protocol -defined parameters
  • No evidence of chronic or acute disseminated intravascular coagulation or bleeding tendency and no angina at rest
  • Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

  • Histologic variants other than adenocarcinoma in the primary tumor
  • More then 2 different prior chemotherapeutic regimens for metastatic prostate cancer
  • Abnormal liver function
  • Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), Ketoconazole, finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (eg, Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug
  • Active infection or intercurrent illness that are not controlled
  • Unstable angina, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, uncontrolled hypertension, New York Heart Association (NYHA) Class III or IV congestive heart failure
  • Prior radiation therapy completed <4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug
  • Any currently active second malignancy, other than non-melanoma skin cancer
  • Active psychiatric illnesses/social situations that would limit compliance with protocol requirements
  • Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
  • Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
  • Acute or chronic hepatitis B or C
  • Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug
  • Long QT syndrome or bundle branch block or hemiblock or other history of life-threatening arrhythmia (unless the patient has been effectively treated for it and is considered stable)
  • Known brain metastasis
  • History of pituitary or adrenal dysfunction
  • History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
  • Prior therapy with abiraterone acetate
  • Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a NCI CTCAE (version 3) grade of <=1
  • Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the 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: NCT00544440

Locations
United States, Texas
Houston, Texas, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00544440     History of Changes
Other Study ID Numbers: CR016906, COU-AA-BMA
Study First Received: October 15, 2007
Results First Received: August 28, 2013
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Prostate neoplasms
Prostate cancer
Castration-resistant prostate cancer
Abiraterone acetate
CB7630
Prednisone
Testosterone
Bone marrow

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Androgens
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014