Abiraterone Acetate in Treating Patients With Hormone-Resistant Prostate Cancer

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentNot specified11-0709
NCI-2012-00116, NCT01543776

Trial Description

Summary

This randomized phase II trial studies the best way to give abiraterone acetate in treating patients with hormone-resistant prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, may lessen the amount of androgen made by the body.

Further Study Information

PRIMARY OBJECTIVES:

I. To compare the pharmacodynamic effect of reduced dose (250mg daily) abiraterone acetate in the prandial state (250mg-Fed) to the full, standard 1000mg daily dose in the fasting state (1000mg-Fasting) as assessed by change in serum prostate-specific antigen (PSA).

SECONDARY OBJECTIVES:

I. To evaluate the effect of prandial states on plasma levels and the intra-patient pharmacokinetic variability of abiraterone acetate.

II. To evaluate the safety profile of reduced dose abiraterone acetate taken in the prandial state.

III. To evaluate the pharmacodynamic effect of reduced dose abiraterone acetate in the prandial state as assessed by reduction in the extra-gonadal androgen dihydroepiadrosterone sulfate (DHEA-S) and dihydroepiandrostenedione (DHEA).

IV. To evaluate the effect of prandial state on time to disease progression (Working group criteria).

V. To assess and describe medication adherence to abiraterone acetate for both dosing schedules.

OUTLINE: Patients are randomized to one of two treatment arms.

ARM I: Patients receive abiraterone acetate orally (PO) daily first thing in morning after an overnight fast of at least 8 hours and prednisone PO twice daily (BID).

ARM II: Patients receive abiraterone acetate PO daily within 30 minutes of a conventional low-fat breakfast and prednisone as in Arm I.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days.

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed prostate cancer with progressive disease defined as either:

2 or more new lesions on bone scan or

Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria or

Rising prostate-specific antigen (PSA): PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart

Evidence of castration resistance defined as disease progression despite a testosterone level < 50 ng/dL (or surgical castration)

Total bilirubin =< 1.5 x the upper limit of normal

Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Any prior therapy for castrate disease is acceptable except prior abiraterone, which is excluded; a minimum washout of 28 days for any other anticancer therapy prior to first dose of study drug is required

Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug

Denosumab or zoledronic acid are allowed

Ability to understand and the willingness to sign a written informed consent document

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal

Exclusion Criteria:

New York Heart Association (NYHA) class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure)

Blood pressure that is not controlled despite > 2 oral agents (systolic blood pressure [SBP] > 160 and diastolic blood pressure [DBP] > 90 documented during the screening period with no subsequent blood pressure readings < 160/100)

Inability to swallow capsules or known gastrointestinal malabsorption

Concurrent therapy with strong inhibitors or inducers of Cytochrome P450 (CYP)3A4 due to concerning possible drug-drug interactions with abiraterone

Active psychiatric illness/social situations that would limit compliance with protocol requirements

Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled

Serum potassium (K)+ < 3.5 mmoL/L on more than one reading within the screening period

History of other malignancies, with the exception of adequately treated non-melanoma skin cancer or adequately treated superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for >= 5 years from enrollment

Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug is excluded with the following exceptions:

Conventional multivitamin supplements

Selenium

Lycopene

Soy supplements

Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid (other than prednisone =< 10 mg/day) within 4 weeks prior to first dose of study drug

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

University of Chicago Comprehensive Cancer Center

  • National Cancer Institute
Russell Zelig Szmulewitz, Principal Investigator

Trial Sites

U.S.A.

Georgia
Atlanta

Emory University/Winship Cancer Institute

Bradley Curtis Carthon
Ph: 404-778-1868
Email: bradley.c.carthon@emory.edu

Bradley Curtis Carthon
Principal Investigator

Illinois
Chicago

Northwestern University

Timothy M. Kuzel
Email: t-kuzel@northwestern.edu

Timothy M. Kuzel
Principal Investigator

University of Chicago Comprehensive Cancer Center

Russell Zelig Szmulewitz
Ph: 773-702-7609
Email: rsmulew@medicine.bsd.uchicago.edu

Russell Zelig Szmulewitz
Principal Investigator

Evanston

NorthShore University HealthSystem-Evanston Hospital

Bruce E. Brockstein
Email: bbrockstein@northshore.org

Bruce E. Brockstein
Principal Investigator

Harvey

Ingalls Memorial Hospital

Mark Farrell Kozloff
Email: mfkozloff@aol.com

Mark Farrell Kozloff
Principal Investigator

Peoria

Illinois CancerCare-Peoria

Sachdev P. Thomas
Email: sthomas@illinoiscancercare.com

Sachdev P. Thomas
Principal Investigator

Springfield

Southern Illinois University School of Medicine

John E. Godwin
Email: jgodwin@siumed.edu

John E. Godwin
Principal Investigator

Indiana
Fort Wayne

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Sreenivasa R. Nattam
Email: ledgar@fwmoh.com

Sreenivasa R. Nattam
Principal Investigator

Michigan
Ann Arbor

University of Michigan Comprehensive Cancer Center

Maha H. A. Hussain
Email: mahahuss@umich.edu

Maha H. A. Hussain
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01543776

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.