18-fluorofuranylnorprogesterone (FFNP) PET/MRI as a Potential Biomarker of Response to Progesterone Therapy

Study Overview
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Brief Summary
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Purpose: The purpose of this study is to evaluate FFNP PET/MRI's utility for predicting response to Levonorgestrel-releasing Intrauterine Device (LR-IUD) hormonal therapy for Complex Atypical hyperplasia (CAH) and Endometrial Cancer (EC). Participants: Eight women with histologically confirmed CAH or Grade 1 EC who have planned treatment with LR-IUD will be recruited.. Procedures (methods): The is a prospective, single arm, pilot study of 8 participants who will receive one FFNP PET/MRI scan. Medical records will be followed for 6 months.

Official Title
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18-fluorofuranylnorprogesterone (FFNP) Positron Emission Tomography-Magnetic Resonance Imaging (PET/MRI) as a Potential Biomarker of Response to Progesterone Therapy in Complex Atypical Hyperplasia (CAH) and Grade 1 Endometrial Cancer (EC)

Conditions
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Complex Atypical Hyperplasia, Endometrial Cancer

Intervention / Treatment
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* Drug: 18F-fluorofuranylnorprogesterone PET / MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female age 18 or older Histologically confirmed CAH or Grade 1 EC No prior surgical or hormonal treatment for CAH or Grade 1 EC Planned treatment with levonorgestrel-releasing intrauterine device (LR-IUD) for CAH or grade 1 EC Exclusion Criteria: Inability to complete PET/MR scans due to severe claustrophobia Institutionalized subject (prisoner or nursing home subject) Implanted metallic devices, parts, vascular clips, or other foreign bodies. Known hypersensitivity to gadolinium or FFNP or to any component of gadolinium or FFNP refractory to standard medications (antihistamines, steroids) Impaired kidney function (serum creatinine level > 1.8 mg/dl or a glomerular filtration rate < 60 as approximated using serum creatinine levels) unless anuric and on dialysis. Any woman who is pregnant or has reason to believe she is pregnant (the possibility of pregnancy has to be excluded by negative urine (β-HCG) results, obtained within 24 hours before FFNP administration, or on the basis of patient history) Prior hormone treatment for breast cancer

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: 18F-fluorofuranylnorprogesterone PET / MRI<br>All enrolled subjects will receive the tracer and then have a PET/MRI scan. | Drug: 18F-fluorofuranylnorprogesterone PET / MRI<br>* Subjects will receive a PET/MRI with 18F-fluorofuranylnorprogesterone tracer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of 18F-fluorofuranylnorprogesterone (FFNP) PET/MRI for predicting response to progestin therapy in CAH /EC patients | The sensitivity of FFNP PET /MR is defined as the ability of readers (radiologists) to correctly detect areas that will respond to treatment, as determined by histopathologic evaluation. | Upon completion of all study image data collection for all participants [approximately 1 year] | 
| Specificity of 18F-fluorofuranylnorprogesterone (FFNP) PET/MRI for predicting response to progestin therapy in CAH /EC patients | The specificity is similarly defined as the ability of readers to determine areas that will fail to respond to treatment, as determined by histopathologic evaluation. | Upon completion of all study image data collection for all participants [approximately 1 year] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate FFNP Mean Standardized Uptake Value (SUVmean) at baseline and on repeat examination with estrogen and progesterone receptor expression in the CAH/EC tissues at baseline and after 6 months of treatment. | The association between SUVmean and tumor volume and the degree of estrogen/progesterone receptor will be evaluated using random coefficient trajectory models, separately for each outcome. These models allow a separate outcome trajectory for each patient, accounting for within-patient correlations arising from the fact that measurements are taken at multiple timepoints. Estrogen/progesterone receptor will be included as a fixed effect, along with the interaction of this fixed effect and time. A p-value <0.05 for this interaction will be considered evidence that the association between the outcome and estrogen/progesterone receptor varies by time. A patient-level random intercept will be included in the models. Differences in predicted means of the outcomes at each time point will be computed and tested to see if they differ from 0; p-values <0.05 for these tests will be considered evidence of a difference in predicted means by estrogen/progesterone values. | Upon completion of all study image data collection for all participants [approximately 1 year] | 
| Correlate FFNP Maximum Standardized Uptake Value (SUVmax) at baseline and on repeat examination with estrogen and progesterone receptor expression in the CAH/EC tissues at baseline and after 6 months of treatment. | The association between SUVmax and tumor volume and the degree of estrogen/progesterone receptor will be evaluated using random coefficient trajectory models, separately for each outcome. These models allow a separate outcome trajectory for each patient, accounting for within-patient correlations arising from the fact that measurements are taken at multiple timepoints. Estrogen/progesterone receptor will be included as a fixed effect, along with the interaction of this fixed effect and time. A p-value <0.05 for this interaction will be considered evidence that the association between the outcome and estrogen/progesterone receptor varies by time. A patient-level random intercept will be included in the models. Differences in predicted means of the outcomes at each time point will be computed and tested to see if they differ from 0; p-values <0.05 for these tests will be considered evidence of a difference in predicted means by estrogen/progesterone values. | Upon completion of all study image data collection for all participants [approximately 1 year] |