F-18 FES PET/CT in Measuring Hormone Expression in Patients With Primary, Recurrent, or Metastatic Breast Cancer Undergoing Endocrine-Targeted Therapy

Study Overview
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Brief Summary
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This clinical trial studies use of F-18 16 alpha-fluoroestradiol ([F-18] FES) positron emission tomography (PET)/computed tomography (CT) in measuring tumor hormone receptor expression in patients undergoing endocrine-targeted therapy for newly diagnosed breast cancer or breast cancer that has come back or spread to other places in the body. Comparing results of diagnostic procedures done before, during, and after hormone therapy may help measure a patient's response to treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Measure the effect of endocrine targeted therapy on estrogen receptor (ER) expression and estradiol binding to the receptor using serial FES PET and fludeoxyglucose F-18 (FDG) PET. SECONDARY OBJECTIVES: I. Document the safety profile of FES PET in patients with breast cancer. II. Examine associations between FES PET results and serial measurements of hormone or other levels in peripheral blood, as related to efficacy of endocrine-targeted therapy. Correlate FES PET uptake measures with histopathological assays and tumor microenvironment studies on biopsy specimens, if relevant to specific treatment regimen. OUTLINE: Patients undergo F-18 FES PET/CT scan at baseline. Patients also undergo F-18 FES PET/CT and FDG PET/CT between 1-12 weeks after starting therapy, and then 1-12 weeks after the second FES PET/CT scan. Repeat FDG PET may be omitted in patients on selective estrogen receptor degrader. After completion of study, patients are followed up for up to 20 years.

Official Title
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Serial [F-18] Fluoroestradiol (FES) PET Imaging to Evaluate Endocrine-Targeted Therapy

Conditions
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Estrogen Receptor Positive, Recurrent Breast Carcinoma, Stage IV Breast Cancer AJCC v6 and v7

Intervention / Treatment
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* Procedure: Computed Tomography
* Procedure: Computed Tomography
* Drug: F-18 16 Alpha-Fluoroestradiol
* Drug: Fludeoxyglucose F-18
* Other: Laboratory Biomarker Analysis
* Procedure: Positron Emission Tomography
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult, non-pregnant patients with biopsy-proven or clinically obvious primary, recurrent or metastatic breast cancer Breast cancer from ER+ primary that is seen on other imaging tests; tumor ER expression must have been confirmed by immunohistocytochemistry of primary tumor or recurrent disease At least one site of disease 1.5 cm or greater is needed to meet the spatial resolution limits of PET imaging Patients must have been off tamoxifen or other estrogen receptor blocking agents for at least 6 weeks and off chemotherapy for 3 weeks for the initial baseline FES Patients must be selected for an endocrine targeted therapy regimen for treatment of their breast cancer by the referring oncologist; selected treatments may be part of experimental treatment protocols for which the patient would be separately consented Patients must be willing to undergo serial imaging procedures Patients must agree to allow access to clinical records regarding response to treatment and long term follow up Exclusion Criteria: An inability to lie still for the tests Individuals weighing more than 300 lb; (this is the weight limit of the scanner table) Pregnant or lactating; women of childbearing potential with either a positive or no pregnancy test at baseline are excluded Any other life-threatening illness (e.g. serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication) Use of tamoxifen, Faslodex, diethylstilbestrol (DES) or any other ER blocking agent < 6 weeks or chemotherapy < 3 weeks prior to imaging scan Unwillingness or inability to give informed consent Uncontrolled diabetes mellitus (fasting glucose > 200 mg/dL) Adult patients who require monitored anesthesia for PET scanning

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: Diagnostic (F-18 FES PET/CT)<br>Patients undergo F-18 FES PET/CT scan at baseline. Patients also undergo F-18 FES PET/CT and FDG PET/CT between 1-12 weeks after starting therapy, and then 1-12 weeks after the second FES PET/CT scan. Repeat FDG PET may be omitted in patients on selective estrogen receptor degrader. | Procedure: Computed Tomography<br>* Undergo F-18 FES PET/CT<br>* Other names: tomography;Procedure: Computed Tomography<br>* Undergo FDG PET/CT<br>* Other names: tomography;Drug: F-18 16 Alpha-Fluoroestradiol<br>* Undergo F-18 FES PET/CT<br>* Other names: Fluoroestradiol F-18;Drug: Fludeoxyglucose F-18<br>* Undergo FDG PET/CT<br>* Other names: Fluorodeoxyglucose F18;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Positron Emission Tomography<br>* Undergo F-18 FES PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;Procedure: Positron Emission Tomography<br>* Undergo FDG PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV | Uptake was quantified using lean body mass adjusted SUV (SULmean). The geometric mean was calculated for up to 3 lesions per patient. Systematic change in FES SULgmean between baseline and a second FES scan at approximately 2 or 8 weeks and a third FES scan was at approximately 8 weeks measured using a sign test where the median change is zero. | from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks) | 
| F-18 16 Alpha-fluoroestradiol (FES) Uptake | Quantitative and qualitative measures of FES uptake for each disease site, a set of 1.5 cm diameter regions on three adjacent planes with the highest lesion FES uptake will be drawn to determine maximal FES uptake. Up to 10 sites seen on the static torso survey will be quantified. Lesions will qualitatively determined to be visible or not visible. | from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks) | 
| Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) | The number of patients showing a 20% increase in FES SULgmean compared to baseline at either 2 or 8 weeks using a 90% Wilson score binomial confidence interval. | from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Months from the start of endocrine therapy to the time the patient is first recorded as having disease progression, | from start of therapy up to 20 years |