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

Phase 2

Withdrawn

• Conditions: Detectable Prostate Nodules
• Interventions: Drug: Bicalutamide plus Finasteride- Combination therapy

• Registration Number: NCT02146937
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-05-01
• Study First Submitted QC: 2014-05-23
• Study First Posted: 2014-05-26
• Primary Completion: 2015-03
• Study Completion: 2015-03
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-20
• Last Update Posted: 2017-03-22

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination therapy- bicalutamide and finasteride	Bicalutamide plus Finasteride- Combination therapy	3-month (90-day) course of bicalutamide 50 mg by mouth daily and finasteride 5 mg by mouth daily

Primary Outcome Measures

Name	Time	Method
Negative re-biopsy rate	three months (90 days)	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.

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States