Evaluation of PSMA in HER2- AR+ Metastatic Breast Cancer

Evaluation of Prostate Specific Membrane Antigen (PSMA) in HER2-negative, Androgen Receptor (AR)-Positive Metastatic Breast Cancer With 18F-DCFPyL PSMA-based PET/CT

The purpose of this research is to determine the expression of prostate specific membrane antigen (PSMA) in human epidermal growth factor receptor 2 (HER2)-negative, androgen receptor (AR)-positive metastatic breast cancer, and to determine its role in resistance to the anti-androgen, bicalutamide. The investigators hypothesize that PSMA expression will correlate with resistance to anti-androgen therapies, as has been documented in prostate cancer, and this can be used to select patients most likely to benefit from these therapies in future clinical trials. 15 people with HER2-negative, AR-positive metastatic breast cancer will be enrolled and be on study for about 3 days.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Metastatic Breast Cancer; HER2-negative Breast Cancer
• Intervention / Treatment: Drug: 18F-DCFPyL

Detailed Description

Primary Objective:

• To evaluate the expression of PSMA via 18F-DCFPyL PSMA-based PET/CT in patients with metastatic HER2-negative, AR-positive breast cancer. Expression of PSMA will be quantified using PSMA-based PET imaging using a novel agent, 18F-DCFPyL, as a non-invasive imaging biomarker of tumor neovasculature in HER2-negative, AR-positive metastatic breast cancer.

Secondary Objectives:

• PSMA PET will be compared with the expression of PSMA in CTCs and diagnostic metastatic tissue from patients with HER2-negative, AR-positive metastatic breast cancer.
• PSMA expression will be correlated with clinical benefit (objective response and progression-free survival) to bicalutamide and ribociclib for patients enrolled in NCT03090165.

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Radiology Studies; Phone Number: 608-282-8349; Email: Radstudy@uwhealth.org

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin School of Medicine and Public Health
      • Contact: Gemma Gliori; Phone Number: 608-262-7269; Email: ggliori@uwhealth.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients diagnosed with metastatic HER2-negative breast cancer AR expression of ≥ 10%

Exclusion Criteria:

• Other (non-breast) known active malignancy. Participants with previously treated cancers which are in remission or have no evidence of disease are eligible.
• Unable to lie flat during or tolerate PET/CT
• Participants with any medical condition or other circumstances that, in the opinion of the investigator, compromise the safety or compliance of the subject to produce reliable data or completing the study
• Women of childbearing potential must not be pregnant or breast feeding (pregnancy test negative within 7 days prior to PET/CT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: 18F-DCFPyL PSMA-based PET/CT; 18F-DCFPyL whole body PET/CT scan; Review of relevant imaging and medical record information; Blood draw for circulating tumor cells (CTCs); Analysis of diagnostic tissue specimens	Drug: 18F-DCFPyL; PSMA is highly expressed on prostate cancer and is associated with metastasis and resistance to anti-androgen therapies. Researchers have evaluated the expression of PSMA in the tumor and tumor-associated neovasculature in primary tumors and distant metastases in patients with breast cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSMA Expression as measured by 18F-DCFPyL SUV	Quantitative analysis of 18F-DCFPyL PSMA PET uptake will be performed at the lesion-level. Standardized uptake values (SUV) will be measured by manually drawing a region of interest (ROI) to encompass the entire lesion guided by the lesion extent visualized on conventional imaging. PET SUV based quantitative tumor uptake parameters will be obtained.	up to 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of PSMA in CTCs	Expression of PSMA in CTCs will be measured via immunofluorescence.	up to 2 weeks
Expression of PSMA in diagnostic metastatic tissue	PSMA expression in tumors will be semi-quantitatively scored by a study pathologist using published methods including separate assessment of tumor-associated and non-tumor vasculature, with the endothelium highlighted by a CD31 immunostain to facilitate definitive recognition.	up to 3 days
Change in PSMA Expression on CTCs after 2 weeks of bicalutamide	The change in PSMA expression on CTCs will be measured pre and post treatment via immunofluorescence.	baseline and up to 2 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Amy Fowler, MD, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: September 28, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid
• Other Study ID Numbers: 2020-0949 (Other Identifier: UW Madison); A539300 (Other Identifier: UW Madison); SMPH/RADIOLOGY/RADIOLOGY (Other Identifier: UW Madison); NCI-2020-07434 (Registry Identifier: NCI CTRP); Protocol Version 12/12/2025 (Other Identifier: UW Madison)

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