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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Detectable Prostate Nodules

Intervention / Treatment
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* Drug: Bicalutamide plus Finasteride- Combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent. Age ≥ 18 years Eastern cooperative group (ECOG) performance status ≤2 Documented histologically confirmed adenocarcinoma of the prostate (minimum 12 core prostate biopsy completed within 90 days of screening) 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 Willing and qualified for active surveillance at Johns Hopkins 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. Serum testosterone ≥150 ng/dL Able to swallow the study drugs whole as a tablet Exclusion Criteria: Prior local therapy to treat prostate cancer (e.g., radical prostatectomy, radiation therapy, brachytherapy) Prior use of bicalutamide Prior use of finasteride within the past year 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) 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. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL] Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal) Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal) 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination therapy- bicalutamide and finasteride<br>3-month (90-day) course of bicalutamide 50 mg by mouth daily and finasteride 5 mg by mouth daily | Drug: Bicalutamide plus Finasteride- Combination therapy<br>* 3-month (90-day) course of bicalutamide 50 mg by mouth daily and finasteride 5 mg by mouth daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative re-biopsy rate | 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. | three months (90 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of exit at 2 years from the active surveillance program at Johns Hopkins due to pathologic upstaging following treatment with bicalutamide plus finasteride. |  | 2 years | 
| PSA progression rates and PSA progression free survival (PFS), as defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, at 2 years [Scher et al, 2008]. |  | 2 years | 
| Rate of radiographic disappearance of MRI detectable prostate cancer following treatment with combination bicalutamide plus finasteride (i.e., decrease in size of the target prostate cancer nodule below 5 mm). |  | 2 years | 
| Adverse events as assessed by the revised National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.0 published 14 June 2010. |  | 2 years | 
| Quality of life utilizing the FACT-P and SF36 surveys |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biopsy, active surveillance, MRI/transrectal ultrasound fusion guided biopsy