A Phase 2 Study of Bicalutamide Plus Finasteride in Men with MRI Detectable Prostate Nodules Undergoing Active Surveillance
To determine if a 3-month course of combination bicalutamide plus finasteride will lead to a negative re-biopsy of MRI detectable significant (i.e., equal to 5mm and biopsy proven to be prostatic adenocarcinoma) prostate nodules in active surveillance patients.
Inclusion Criteria: 1.Willing and able to provide written informed consent. 2.Age equal to 18 years. 3.Eastern cooperative group (ECOG) performance status equal to 2. 4.Documented histologically confirmed adenocarcinoma of the prostate (minimum 12 core prostate biopsy completed within 90 days of screening). 5.Very low-risk prostate cancer as defined by: a.Gleason score equal to 6 b.PSA density equal to 0.15 ng/mL/mL c.PSA less than 10 ng/mL d.Clinical tumor stage T1 (cT1) (i.e., no palpable nodule by digital rectal exam) e. equal to 2 prostate cores positive for prostatic adenocarcinoma f. equal to 50% of any given core involved by prostatic adenocarcinoma. 6.Willing and qualified for active surveillance at Johns Hopkins. 7.Presence of at least one MRI significant visible prostate tumor (i.e., equal to 5 mm in at least one dimension) that has been biopsy proven to be prostatic adenocarcinoma. Note: MRI may occur pre- or post-prostate biopsy. MRI may occur between 0 and 180 days prior to prostate biopsy. If done post-biopsy, the MRI must not occur less than 8 weeks post-prostate biopsy. 8.Serum testosterone equal to 150 ng/dL. 9.Able to swallow the study drugs whole as a tablet. Exclusion Criteria: 1.Prior local therapy to treat prostate cancer (e.g., radical prostatectomy, radiation therapy, brachytherapy). 2.Prior use of bicalutamide. 3.Prior use of finasteride within the past year. 4.Prior or ongoing systemic therapy for prostate cancer including, but not limited to: a.Hormonal therapy (e.g., leuprolide, goserelin, triptorelin) b.CYP-17 inhibitors (e.g., abiraterone, ketoconazole) c.Antiandrogens (e.g., bicalutamide, flutamide, nilutamide) d.Second generation antiandrogens (e.g., enzalutamide, ARN-509) e.Immunotherapy (e.g., sipuleucel-T, ipilimumab) f.Chemotherapy (e.g., docetaxel, cabazitaxel). 5.Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study. 6.Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule. 7.Abnormal bone marrow function [absolute neutrophil count (ANC) less than 1500/mm3, platelet count less than 100,000/mm3, hemoglobin less than 9 g/dL]. 8.Abnormal liver function (bilirubin, AST, ALT equal to 3 x upper limit of normal). 9.Abnormal kidney function (serum creatinine equal to 2 x upper limit of normal). 10.Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years prior to enrollment in the study.
Study Design: This is an open label, single site, single arm Phase II study to evaluate the combination of bicalutamide plus finasteride in men with MRI detectable significant prostate nodules followed on active surveillance. Treatment Plan: This is an open label, single site, single arm Phase II study designed to determine the negative re-biopsy rate of prostate cancer nodules as determined by an MRI/transrectal ultrasound (TRUS) fusion guided biopsy following treatment with combination bicalutamide and finasteride in men enrolled in the active surveillance program at Johns Hopkins. Eligible patients will receive a 3-month (90 day) course of bicalutamide 50 mg by mouth daily and finasteride 5 mg by mouth daily. These doses were selected given that they are the current Food and Drug Administration (FDA) approved single-agent doses. Enrolled subjects will receive 90 days of combination therapy.
09/23/2014 04:03 AM