A Phase 2 Study of Bicalutamide Plus Finasteride in Men With MRI Detectable Prostate Nodules Undergoing Active Surveillance

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.

This research is being done to determine the negative re-biopsy rate as determined by MRI/TRUS fusion guided biopsy targeting the dominant nodule site defined by pre-treatment MRI following three months (90 days) of combination bicalutamide plus finasteride.

Eligibility Criteria:
Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Age ≥ 18 years
3. Eastern cooperative group (ECOG) performance status ≤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:

   * Gleason score ≤ 6
   * PSA density ≤ 0.15 ng/mL/mL
   * PSA \< 10 ng/mL
   * Clinical tumor stage T1 (cT1) (i.e., no palpable nodule by digital rectal exam)
   * ≤2 prostate cores positive for prostatic adenocarcinoma
   * ≤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., ≥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. If done post-biopsy, the MRI must not occur \<8 weeks post-prostate biopsy.
8. Serum testosterone ≥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:

   * Hormonal therapy (e.g., leuprolide, goserelin, triptorelin)
   * CYP-17 inhibitors (e.g., abiraterone, ketoconazole)
   * Antiandrogens (e.g., bicalutamide, flutamide, nilutamide)
   * Second generation antiandrogens (e.g., enzalutamide, ARN-509)
   * Immunotherapy (e.g., sipuleucel-T, ipilimumab)
   * 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 \[absolute neutrophil count (ANC)\<1500/mm3, platelet count \<100,000/mm3, hemoglobin \<9 g/dL\]
8. Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal)
9. Abnormal kidney function (serum creatinine ≥ 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.