Assessing Induction of Double Strand Breaks With Androgen Receptor Partial Agonist in Patients on Androgen Suppression

Randomized Trial Assessing Induction of Double Strand Breaks With Androgen Receptor Partial Agonist in Patients on Androgen Suppression

This is a prospective, single-center, two-phase study to assess the efficacy of single pulsed-dose flutamide in creating double strand breaks (DSBs) in prostate cancer within patients receiving central androgen suppression and brachytherapy.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Flutamide; Other: Placebo

Detailed Description

This is a prospective, single-center, two-phase study to assess the efficacy of single pulsed-dose flutamide in creating DSBs (double strand breaks) in prostate cancer within patients receiving central androgen suppression and brachytherapy. The initial phase is a 6-patient single-arm run-in phase to test feasibility and rule out futility of the intervention. All patients within the run-in phase will receive 50mg flutamide prior to brachytherapy and prostatic biopsy. If futility is ruled out (>1 patients with DSBs on biopsy), then accrual will continue in the randomized, double-blind phase. Subjects will be randomized in a 2:1 ratio (12:6 patients), for an all-trial total of 18 patients receiving flutamide vs 6 patients receiving placebo.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Daniel Song, M.D.; Phone Number: 410-502-5875; Email: dsong2@jhmi.edu
• Study Contact Backup: Name: Shirley DiPasquale, R.N.; Phone Number: 410-614-1598; Email: sdipasq1@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • SKCCC at Johns Hopkins
      • Contact: Daniel Song, M.D.; Phone Number: 410-502-5875; Email: dsong2@jhmi.edu
      • Contact: Shirley DiPasquale, R.N; Phone Number: 410-614-1598; Email: sdipasq1@jhmi.edu
      • Sub-Investigator: Srinivasan Yegnasubramanian, M.D., Ph.D.
      • Sub-Investigator: Jonathan Coulter, M.D.
      • Sub-Investigator: Angelo Demarzo, M.D.
      • Sub-Investigator: Chen Hu, Ph.D.
      • Sub-Investigator: Theodore DeWeese, M.D.
      • Sub-Investigator: Michael Gorin, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed prostate cancer
• At least one biopsy core with Gleason 7 or higher disease
• The patient has decided to undergo brachytherapy plus androgen suppression as treatment modality for his prostate cancer (with or without supplemental external beam radiation)
• Suitable volume of disease for biopsy:
• clinically palpable disease corresponding to (ipsilateral to) any involved core on biopsy
• Signed study-specific consent form prior to registration

Exclusion Criteria:

• Known hypersensitivity or allergic response to flutamide
• Severe hepatic impairment
• Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: flutamide; 50mg flutamide prior to brachytherapy and prostatic biopsy	Drug: Flutamide; 50mg flutamide prior to brachytherapy and prostatic biopsy
Placebo Comparator: placebo; placebo prior to brachytherapy and prostatic biopsy	Other: Placebo; placebo prior to brachytherapy and prostatic biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to DNA double strand break	To confirm DNA double strand breaks occur in prostate cancer tissue following pulse-dose flutamide administration in patients who are androgen suppressed, as compared to control patients receiving placebo.	6-9 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Daniel Song, M.D., SKCCC at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2019
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: April 16, 2018
• First Posted (Actual): April 25, 2018

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgen Antagonists; Flutamide
• Other Study ID Numbers: J1851; IRB00167697 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No