Biomarkers of Androgen Response and Resistance In Evolution During a Rising PSA (BARRIER-P)

University Health Network, Toronto

Status and phase

Completed

Phase 2

Conditions

Castration-resistant Prostate Cancer

Treatments

Drug: Enzalutamide

Drug: Abiraterone + prednisone

Study type

Interventional

Funder types

Other

Identifiers

NCT02429193

BARRIER-P

Details and patient eligibility

About

This is an open-label phase 2 multi-center study of abiraterone and enzalutamide in men with castration-resistant prostate cancer. Sixteen patients will be enrolled over 18 months.

Enrollment

16 estimated patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with histologically or cytologically confirmed prostate cancer
Able to read and understand the consent form, either alone or with the aid of a translator
Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nmol/L). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patients who have not undergone orchiectomy), they must remain on continuous androgen suppression therapy throughout the study
Patients receiving bone-targeted therapies must be on stable doses for at least 4 weeks prior to enrollment
Historical frozen/paraffin-embedded diagnostic tissue specimens are available for analysis (i.e. radical prostatectomy or biopsy tissue)
Documented metastatic disease by positive bone scan or metastatic lesions (on CT or MRI) that can be biopsied with an anticipated minimum of 4 cores, as assessed by the local radiologist
prostate cancer progression at study entry defined as one or more of the following criteria: i. Rising PSA: minimum of two rising PSA levels with an interval of ≥ 1 week between each determination ii. Soft tissue disease progression, as defined by RECIST 1.1 iii. Bone disease progression, as defined by PCWG2 with two or more new lesions on bone scan
PSA value at screening visit ≥ 2 µg/L (2 ng/mL)
ECOG performance status 0-2
Adequate organ and BM function, as defined by the following criteria:

i. absolute neutrophil count ≥1,500/µL ii. platelets ≥100,000/µL iii. total bilirubin ≤1.5 × institutional upper limit of normal (ULN) iv. AST(SGOT) or ALT(SGPT) ≤2.5 × institutional ULN v. creatinine ≤1.5 × institutional ULN or below
Serum albumin ≥ 3.0 g/dL
Serum potassium ≥ 3.5 mmol/L
Haemoglobin ≥ 10.0 g/dL, independent of transfusion
Asymptomatic or mildly symptomatic from prostate cancer
Life expectancy of > 6 months
Able to swallow study drugs
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 13 weeks after last study drug administration

Exclusion criteria

Patients with known hypersensitivity or allergy to abiraterone acetate, enzalutamide or any of their excipients.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (NYHA Class 3 or greater), cirrhosis with a Child-Pugh level of B or greater or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 6 months, hypotension (defined by systolic blood pressure < 86 mmHg at Screening visit), hypertension (defined by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at Screening visit), bradycardia (defined by < 50 beats per minute on ECG performed at screening), active peptic ulcer disease, clinically significant gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis), any seizure disorder or psychiatric illness, and social situations that would limit compliance with study requirements
Active invasive malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
Known or suspected brain metastasis or leptomeningeal disease
Radiotherapy within the past 4 weeks, except for low dose palliative radiation to bone of ≤5 fractions
Treatment with 5-α reductase inhibitors (finasteride, dutasteride), androgen receptor antagonists (bicalutamide, nilutamide, flutamide), estrogens, cyproterone within 4 weeks of Day 1 visit