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

Study Description

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Brief Summary:

This phase II trial studies how well abiraterone acetate works in treating patients with hormone-resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic). Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease	Intervention/treatment	Phase
Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Adenocarcinoma	Drug: Abiraterone Acetate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Prednisone	Phase 2

Detailed Description:

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 (abiraterone acetate) at 1000 mg twice daily.

OUTLINE:

Patients receive abiraterone acetate orally (PO) once daily (QD) 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	28 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer
Actual Study Start Date :	December 2012
Actual Primary Completion Date :	September 12, 2017
Actual Study Completion Date :	September 12, 2017

Arms and Interventions

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Arm

Intervention/treatment

Experimental: Treatment (abiraterone acetate and prednisone); Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Abiraterone Acetate; Given PO; Other Names: CB7630; Zytiga Other: Laboratory Biomarker Analysis; Correlative studies Other: Pharmacological Study; Correlative studies Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisonum; Prednitone; Promifen; Servisone; SK-Prednisone

Outcome Measures

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Primary Outcome Measures :

1. Change in tissue testosterone, dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA) [ Time Frame: From baseline to week 4 ]
   Tissue testosterone, DHT, androstenedione, and DHEA measurements will be summarized numerically and graphically using plots of patient- and cohort-specific longitudinal patterns and side-by-side boxplots at each time point. A 2-sided paired t-test will be used and an attained significance level of 5% will be considered statistically significant.

Secondary Outcome Measures :

1. Ability of abiraterone acetate to suppress tumor testosterone, assessed by changes in testosterone levels [ Time Frame: From baseline to 12 weeks ]
2. 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 ]
3. 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 criteria [ Time Frame: Up to 4 years ]
   The subsequent response to dose escalation (if any) will be correlated with tumor androgens.
4. 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 ]
   Candidate miRNA strongly associated with response or progression will be quantitated in biopsy tissue as possible.
5. Tissue testosterone from metastasis at time of progression [ Time Frame: Up to 4 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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 lines 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)
• Bilirubin levels < 1.5 x 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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109

Sponsors and Collaborators

University of Washington

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Robert Montgomery	Fred Hutch/University of Washington Cancer Consortium

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of Washington
ClinicalTrials.gov Identifier:	NCT01503229 History of Changes
Obsolete Identifiers:	NCT01508234
Other Study ID Numbers:	7639; NCI-2011-03745 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 0801; 7639 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ); P30CA015704 ( U.S. NIH Grant/Contract )
First Posted:	January 2, 2012
Last Update Posted:	January 19, 2018
Last Verified:	January 2018

Additional relevant MeSH terms:

Prostatic Neoplasms; Carcinoma; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Prostatic Diseases; Cortisone acetate; Prednisone; Cortisone	Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors