Evaluation of PSMA in HER2- AR+ Metastatic Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, HER2-negative Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: 18F-DCFPyL


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 2, single-center, open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-DCFPyL PSMA-based PET/CT<br>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<br>* 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.<br>|

What is the study measuring?
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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 |