Clinical trial NCT01940276: Abiraterone Race in Metastatic Castrate-resistant Prostate Cancer
Official title: A Phase II Open-label, Parallel Group Study of Abiraterone Acetate Plus Prednisone in African American and Caucasian Men With Metastatic Castrate-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Prostate cancer
metastatic
castrate resistant
abiraterone acetate
prednisone
metastatic prostate cancer
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2013-09-12
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary goal is to prospectively estimate the median radiographic PFS of African American and Caucasian men with mCRPC to abiraterone acetate and prednisone.

Detailed description: This is a non-comparative pilot open-label, parallel arm, multicenter study of abiraterone acetate in African American and Caucasian men with mCRPC. Patients will self-report on race and 50 patients will be enrolled into each group. Patients will be treated on open-label treatment until evidence of disease progression as defined by Prostate Cancer Working Group Two (PCWG2) definition or until two years at which point they will roll over to the standard of care at that time. The study agent abiraterone acetate will be administered by the patient at a dose of 1000mg orally once daily with prednisone 5 mg BID in 4-week cycles throughout the treatment period.

Eligibility criteria: Inclusion Criteria:

* Male, age ≥ 18 years
* Karnofsky performance status ≥ 70
* Life expectancy of ≥ 12 months
* 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, and should be able to swallow tablets whole, without crushing/chewing tablets
* 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
* Adequate laboratory parameters
* Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are excluded
* Radiographic evidence of metastatic disease; evaluable non-target lesions and/or bone only metastasis are permitted
* Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed. Screening serum testosterone must be \<50 ng/dl
* PSA ≥ 2.0 ng/mL
* Evidence of of castration resistant disease on ADT as evidenced by one of the following:

  * Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR
  * 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR
  * CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to modified PCWG2 criteria or modified RECIST 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies)
* A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide)
* A minimum of 4 weeks elapsed off of sipuleucel-T prior to start of study drug
* A minimum of 4 weeks from any major surgery prior to start of study drug
* Self-reported race of either African American or Caucasian
* Ability to swallow, retain, and absorb oral medication

Exclusion Criteria:

* Prior treatment with abiraterone acetate or enzalutamide
* Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
* Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid
* Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
* Pathological finding consistent with small cell carcinoma of the prostate
* Symptomatic Liver or visceral organ metastasis
* Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
* Known brain metastasis
* Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC
* Previously treated with ketoconazole for prostate cancer for greater than 7 days
* Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
* Uncontrolled hypertension (systolic 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.
* Poorly controlled diabetes
* 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 therapy
* Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
* Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
* Any condition which, in the opinion of the investigator, would preclude participation in this trial

Primary outcomes:
measure: Median Radiographic Progression Free Survival (PFS)
timeFrame: up to 2 years
Secondary outcomes:
measure: Change in PSA Response
timeFrame: Baseline and up to 2 years
measure: Median Time to PSA Progression
timeFrame: up to 2 years
measure: Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml
timeFrame: up to 2 years
measure: Percent of Subjects Experiencing Hypertension
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Medical Center
state: Alabama
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Henderson
country: United States
facility: Maria Parham Medical Center
state: North Carolina
city: Laurinburg
country: United States
facility: Scotland Memorial Hospital
state: North Carolina
city: Lumberton
country: United States
facility: Southeastern Regional
state: North Carolina
city: Raleigh
country: United States
facility: Duke Raleigh Hospital
state: North Carolina
city: Salisbury
country: United States
facility: W. G. 'Bill' Hefner VA Medical Center
state: North Carolina
city: Smithfield
country: United States
facility: Johnston Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional
state: South Carolina
city: Hampton
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
affiliation: Duke University
name: Daniel George, MD
role: PRINCIPAL_INVESTIGATOR
References: