Biomarkers to Detect Endocrine Therapy Resistance

Study Overview
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Brief Summary
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This pilot observational study is being done to identify possible biomarkers of response to endocrine therapy in patients with ER/PR+ metastatic lobular breast cancer (LBC) starting new endocrine therapy. 18F-fluorofuranylnorprogesterone Positron Emission Tomography/Computed Tomography (FFNP-PET/CT) and liquid biopsies will be performed at baseline and after 4 weeks of treatment. Baseline levels and dynamic on-treatment changes in estrogen signaling as measured by FFNP-PET/CT and circulating tumor cell (CTC) liquid biopsy will be correlated with clinical response to endocrine therapy and progression-free survival in the above cohort of patients.

Official Title
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Integrating Minimally Invasive Biomarkers of Estrogen Signaling to Detect Endocrine Therapy Resistance in Metastatic Invasive Lobular Breast Cancer

Conditions
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Metastatic Cancer, Breast Cancer, Lobular Breast Carcinoma

Intervention / Treatment
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* Drug: 18F-fluorofuranylnorprogesterone
* Device: Liquid Biopsy
* Device: Positron Emission Tomography/Computed Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to provide informed consent Individuals at least 18 years of age Have biopsy-proven ER/PR-positive (defined as ER ≥1 percent and PR ≥1 percent by IHC) and HER2-negative advanced or metastatic LBC starting new standard of care endocrine therapy Adequate organ function as indicated by standard laboratory tests (CBC, liver function tests or CMP) allowing for systemic breast cancer treatment per treating oncologist Patients with evaluable bone-only disease that is lytic or mixed lytic-sclerotic are eligible Willing to comply with all study procedures and be available for the duration of the study Disease may be measurable by RECIST 1.1 criteria or non-measurable. Lesion size must be at least 1cm. If only bone lesions present, they should be lytic or mixed lytic-sclerotic. If only liver lesions present, patient is not eligible. Exclusion Criteria: Patients with active brain metastases Patients with liver-only disease are not eligible due to high background liver activity related to the radiopharmaceutical's hepatobiliary route of elimination Unable to lie flat during or tolerate PET/CT Patients with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP Presence of liver failure as judged by patient's treating physician Individuals who are pregnant, lactating, or planning on becoming pregnant during the study Not suitable for study participation due to other reasons at the discretion of the investigators Patients with progesterone-receptor negative disease defined as PR <1 percent by IHC

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with ER/PR+ metastatic lobular breast cancer (LBC)<br> | Drug: 18F-fluorofuranylnorprogesterone<br>* The dose of the investigational imaging agent, FFNP, is approximately 7 millicurie (mCi) (259 megabecquerels (MBq)), IV slow infusion over approximately two minutes followed by saline flush.<br>* Other names: FFNP;Device: Liquid Biopsy<br>* 20ml of whole blood will be collected into two Ethylenediaminetetraacetic acid (EDTA) tubes at each timepoint, CTCs are isolated using the microfluidic Versatile Exclusion-based Rare Sample Analysis (VERSA) platform that integrates CTC capture with RNA extraction on a single chip using Exclusion-Based Sample Preparation (ESP) technology<br>* Other names: Circulating Tumor Cells (CTC);Device: Positron Emission Tomography/Computed Tomography<br>* FFNP drug in combination with PET/CT scans to image participant<br>* Other names: PET/CT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who have decreased FFNP uptake on PET/CT in response to endocrine therapy |  | baseline, 4 weeks | 
| Number of Participants who have decrease in circulating tumor cell estrogen signaling in response to endocrine therapy | Baseline level and on-treatment CTC ESR1 and estrogen regulated gene expression will be evaluated as well as endocrine-resistance associated mutations including ESR1 (though rare in this patient population) and PGR. | baseline, 4 weeks | 
| Number of Participants who have a decrease in concentration of Circulating Tumor DNA in response to endocrine therapy |  | baseline, 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) for 6 months |  | up to 6 months | 
| Correlation coefficients | Correlate baseline levels and dynamic on treatment changes in estrogen signaling as measured by FFNP-PET/CT and CTC liquid biopsy with clinical response to endocrine therapy and progression-free survival in patients with ER/PR+ metastatic LBC. | up to 6 months | 
| Adverse Events within 24 hours of FFNP infusion |  | a 24 hour period up to 7 days pre-treatment, a 24 hour period 4 weeks after the first infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endocrine Therapy Resistance, circulating tumor cell, liquid biopsy