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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01503229
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Location: 1
• Arm: 1
• Actual Duration (Months): 87.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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:

1. 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.

OUTLINE:

Patients receive abiraterone acetate orally once daily and prednisone twice daily 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

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• 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: Dec 1, 2012
• Actual Primary Completion Date: Mar 12, 2020
• Actual Study Completion Date: Mar 12, 2020

Arms and Interventions

Arm

Intervention/Treatment

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

Drug: Abiraterone Acetate; Given by mouth; 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

Primary Outcome Measures

1. Change in Tissue Testosterone and Dihydrotestosterone [From baseline to week 4]

   Tissue testosterone will be measured in biopsy tissues

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 18, 2017

More Information

Publications

None provided.

• Responsible Party: Bruce Montgomery, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT01503229
• Other Study ID Numbers: 7639; NCI-2011-03745; 0801; 7639; P30CA015704; NCT01508234
• First Posted: Jan 2, 2012
• Last Update Posted: May 14, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Carcinoma; Prostatic Neoplasms; Prednisone; Cortisone; Abiraterone Acetate

Study Results

Participant Flow

Arm/Group Title	Treatment (Abiraterone Acetate and Prednisone)
Arm/Group Description	Patients receive abiraterone acetate daily and prednisone twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given orally Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Prednisone: Given orally
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Abiraterone Acetate and Prednisone)
Arm/Group Description	Patients receive abiraterone acetate daily and prednisone twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given orally Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Prednisone: Given orally
Overall Participants	29
Age, Customized (years) [Median (Full Range) ]
Age of participants	71
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	29 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.9%
Not Hispanic or Latino	27 93.1%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 6.9%
White	25 86.2%
More than one race	0 0%
Unknown or Not Reported	2 6.9%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Change in Tissue Testosterone and Dihydrotestosterone
Description	Tissue testosterone will be measured in biopsy tissues
Time Frame	From baseline to week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Abiraterone Acetate and Prednisone)
Arm/Group Description	Patients receive abiraterone acetate daily and prednisone twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given orally Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Prednisone: Given orally
Measure Participants	29
Median (95% Confidence Interval) [pg/mg]	0.156

Adverse Events

Time Frame	Serious adverse events only were collected over the duration of the study from enrollment through disenrollment for the last patient. Total maximum time on study was 2 years.
Adverse Event Reporting Description	No adverse events beyond SAE were collected given that the medication was standard of care. SAE were tracked related to any morbidity related to biopsy
Arm/Group Title	Treatment (Abiraterone Acetate and Prednisone)
Arm/Group Description	Patients receive abiraterone acetate orally once daily and prednisone orally twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Abiraterone Acetate: Given by mouth Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Prednisone: Given by mouth
All Cause Mortality
	Treatment (Abiraterone Acetate and Prednisone)
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Serious Adverse Events
	Treatment (Abiraterone Acetate and Prednisone)
	Affected / at Risk (%)	# Events
Total	0/29 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Abiraterone Acetate and Prednisone)
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.