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

Prostate Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00544440
• Other study ID #: CR016906
• Secondary ID: COU-AA-BMA
• Status: Completed
• Phase: Phase 2
• First received: October 15, 2007
• Last updated: July 3, 2014
• Start date: October 2007
• Est. completion date: August 2012

Study information

• Verified date: July 2014
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Prostate Neoplasms
• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone acetate
Abiraterone 1000 mg (4 x 250 mg tablets) taken orally once daily
• Prednisone
Prednisone 5 mg tablet taken orally twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Detectable Bone Marrow Testosterone Level (>1 Picograms/Mililiter)		Baseline (predose Week 1 Day 1) and Week 8	No
Primary	Number of Participants With Detectable Bone Marrow Dihydrotestosterone (DHT) Level (>9 Picograms/Mililiter)		Baseline (predose Week 1 Day 1) and Week 8	No
Primary	Difference in Bone Marrow Testosterone Levels Between Participants With and Without Serum Prostate Specific Antigen Decline		Week 8	No
Secondary	Number of Participants With Change in Markers of Bone Metabolism		Week 8	No

External Links

•   NATIONAL CANCER INSTITUTE
•   NATIONAL INSTITUTE OF HEALTH