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.

Study Overview

• Status: Withdrawn
• Conditions: Detectable Prostate Nodules
• Intervention / Treatment: Drug: Bicalutamide plus Finasteride- Combination therapy

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy- bicalutamide and finasteride; 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; 3-month (90-day) course of bicalutamide 50 mg by mouth daily and finasteride 5 mg by mouth daily

What is the study measuring?

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	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

Other Outcome Measures

Outcome Measure	Time Frame
Overall rate of exit at 2 years from the active surveillance program at Johns Hopkins following treatment with bicalutamide plus finasteride.	two years
Rate of local treatment (e.g., radical prostatectomy, radiation therapy, brachytherapy) at 2 years and the local treatment free survival	2 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Kenneth Pienta, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: May 1, 2014
• First Submitted That Met QC Criteria: May 23, 2014
• First Posted (Estimate): May 26, 2014

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 20, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: active surveillance; biopsy; MRI/transrectal ultrasound fusion guided biopsy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Androgen Antagonists; 5-alpha Reductase Inhibitors; Bicalutamide; Finasteride
• Other Study ID Numbers: J1408; NA_00092522 (Other Identifier: JHMIRB)