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
Condition: Prostate Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: Abiraterone acetate; Prednisone
Intervention description: Abiraterone 1000 mg (4 x 250 mg tablets) taken orally once daily; Prednisone 5 mg tablet taken orally twice daily
Intervention MeSH terms: Prednisone; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Prostate neoplasms; Prostate cancer; Castration-resistant prostate cancer; Abiraterone acetate; CB7630; Prednisone; Testosterone; Bone marrow

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).
    

Eligibility 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