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Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer


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.


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 and associate response
to tumor androgen levels prior to dose escalation.

IV. To determine potential mechanisms of resistance to abiraterone acetate by analyzing
tissue androgen levels at baseline and at 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.


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.

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

- 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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Change in tissue testosterone, dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA)

Outcome Description:

A 2-sided paired t-test will be used and an attained significance level of 5% will be considered statistically significant.

Outcome Time Frame:

From baseline to week 4

Safety Issue:


Principal Investigator

Robert Montgomery

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

December 2012

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109