Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01503229
First received: December 27, 2011
Last updated: July 28, 2014
Last verified: July 2014

December 27, 2011
July 28, 2014
December 2012
January 2017   (final data collection date for primary outcome measure)
Change in tissue testosterone, dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA) [ Time Frame: From baseline to week 4 ] [ Designated as safety issue: No ]
A 2-sided paired t-test will be used and an attained significance level of 5% will be considered statistically significant.
  • Ability of abiraterone acetate to suppress tumor testosterone, DHT, androstenedione, and DHEA [ Time Frame: Baseline, week 4, week 12, and at progression ] [ Designated as safety issue: No ]
  • Ability of abiraterone acetate to suppress tumor testosterone [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
    Comparisons will be performed with patient's pretreatment tumor biopsy. Statistical assumptions are based on the anticipated change from baseline to one month.
  • Confirmation of tissue-based mechanism of action using tissue androgens at progression on treatment [ Time Frame: 1 or 3 months, or at progression ] [ Designated as safety issue: No ]
    Comparisons will be performed with patient's pretreatment tumor biopsy. Statistical assumptions are based on the anticipated change from baseline to one month.
Complete list of historical versions of study NCT01503229 on ClinicalTrials.gov Archive Site
  • Ability of abiraterone acetate to suppress tumor testosterone, assessed by changes in testosterone levels [ Time Frame: From baseline to 12 weeks ] [ Designated as safety issue: No ]
  • Tissue testosterone from metastasis at time of progression [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • PSA response to dose escalation of abiraterone acetate, defined as decline from the PSA at initiation of therapy and with dose escalation of abiraterone acetate, assessed using Prostate Cancer Working Group 2 (PCWG2) criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The subsequent response to dose escalation (if any) will be correlated with tumor androgens.
  • Potential mechanisms of resistance to abiraterone acetate, determined by assessment of changes in tissue androgen levels, evaluating wild type and splice variant AR levels, and cDNA microarray [ Time Frame: Baseline and time of progression, up to 4 years ] [ Designated as safety issue: No ]
  • Reflection of molecular changes in tumor metastases by microRNA (miRNA) acquired from peripheral blood [ Time Frame: From baseline to time of progression, up to 4 years ] [ Designated as safety issue: No ]
    Candidate miRNA strongly associated with response or progression will be quantitated in biopsy tissue as possible.
  • Response to dose escalation of abiraterone acetate and association with tumor androgen levels prior to dose-escalation [ Time Frame: Every 4 weeks by PSA and every 12 weeks with CT and bone scan ] [ Designated as safety issue: No ]
  • Potential mechanisms of resistance to abiraterone acetate [ Time Frame: Baseline and time of progression ] [ Designated as safety issue: No ]
  • Reflection of molecular changes in tumor metastases by circulating tumor cells (CTC) acquired from peripheral blood [ Time Frame: Baseline, 4 weeks, and 12 weeks or progression ] [ Designated as safety issue: No ]
  • Reflection of molecular changes in tumor metastases by microRNA acquired from peripheral blood [ Time Frame: Baseline, 4 weeks, and 12 weeks or progression ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer.

This phase II trial studies how well giving abiraterone acetate works in treating patients with metastatic hormone-resistant prostate cancer. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the magnitude of tissue testosterone suppression by abiraterone acetate in metastatic castrate-resistant prostate cancer (CRPC) (resistant to luteinizing hormone-releasing hormone [LHRH] agonist or orchiectomy ± antiandrogen) after one month of treatment to establish tissue based mechanism of action.

SECONDARY OBJECTIVES:

I. To determine the ability of abiraterone acetate to suppress tumor testosterone after 12 weeks of treatment.

II. To determine tissue testosterone from metastasis at time of progression during abiraterone acetate treatment.

III. To determine response to dose escalation of abiraterone acetate at clinical progression.

IV. To determine potential mechanisms of resistance to abiraterone acetate by analyzing pharmacokinetics at clinical progression, tissue androgen levels at baseline and at radiographic progression, evaluating wild type and splice variant androgen receptor (AR) levels at baseline and at time of progression and complementary deoxyribonucleic acid (cDNA) microarray at progression.

V. To determine if micro-ribonucleic acid (RNA) acquired from peripheral blood reflect molecular changes in tumor metastases and are a potential biomarker for mechanisms of sensitivity and resistance.

VI. To evaluate pharmacokinetics of dose escalated abiraterone at 1000 mg twice daily.

OUTLINE:

Patients receive abiraterone acetate orally (PO) once daily (QD) on days 1-28 and prednisone PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Drug: abiraterone acetate
    Given PO
    Other Names:
    • CB7630
    • Zytiga
  • Drug: prednisone
    Given PO
    Other Names:
    • DeCortin
    • Deltra
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
Experimental: Treatment (abiraterone acetate and prednisone)
Patients receive abiraterone acetate PO QD on days 1-28 and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: abiraterone acetate
  • Drug: prednisone
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
Not Provided
January 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study
  • Written authorization for use and release of health and research study information has been obtained
  • Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
  • Able to swallow the study drug whole as a tablet
  • Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
  • Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate
  • Histologically proven adenocarcinoma of the prostate
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Metastatic castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following:

    • Prostate specific antigen (PSA) level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
    • Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors)
    • Progression of metastatic bone disease on bone scan with > 2 new lesions
  • Maintenance of Lupron or antagonist unless previously treated with orchiectomy
  • The presence of metastatic disease amenable to computed tomography (CT) or ultrasound guided biopsy; this may include thoracolumbar vertebral bodies, pelvis, femur or humerus, or soft tissue or nodal metastasis amenable to biopsy (excluding lung or pleural lesions)
  • Patients may have received secondary hormonal manipulations (excluding prior Abiraterone acetate, MDV3100 or TAK700) or up to two cycles of chemotherapy; all prior therapy except Lupron must have been discontinued for more than 4 weeks before enrollment
  • Serum potassium of >= 3.5 mEq/L
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN)
  • Serum albumin of >= 3.0 g/dL
  • Total bilirubin =< 1.5 x ULN
  • Calculated creatinine clearance >= 60 mL/min
  • Platelet count of >= 100,000/uL
  • Absolute neutrophil count of > 1,500 cell/mm^3
  • Hemoglobin >= 9.0 g/dL

Exclusion Criteria:

  • Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
  • Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible
  • Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible
  • Known brain metastasis
  • Uncontrolled hypertension (systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
  • Active or symptomatic viral hepatitis or chronic liver disease
  • History of pituitary or adrenal dysfunction
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
  • Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
  • Administration of an investigational therapeutic within 30 days of screening
  • Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent will not be eligible
  • Patients with any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
  • Patients requiring therapeutic anticoagulation (e.g., warfarin, Dabigatran, heparin, or low molecular weight heparins [Lovenox, dalteparin])
  • Patients with poorly controlled diabetes
  • Patients with a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
  • Patients with a pre-existing condition that warrants long-term corticosteroid use in excess of study dose
  • Patients with known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
  • Child-Pugh class B or C hepatic impairment
Male
18 Years and older
No
United States
 
NCT01503229
7639, NCI-2011-03745, P30CA015704
Yes
University of Washington
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Robert Montgomery Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
University of Washington
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP