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

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)

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.

Study Overview

• Status: Withdrawn
• Conditions: Endometrial Cancer; Complex Atypical Hyperplasia
• Intervention / Treatment: Drug: 18F-fluorofuranylnorprogesterone PET / MRI

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
      • Contact: Louis Murphy; Phone Number: 919-966-2544; Email: louis_murphy@med.unc.edu
      • Sub-Investigator: Victoria Bae-Jump, MD
      • Contact: Markeela Lipscomb, CCRC; Phone Number: 919-843-3670; Email: markeela_lipscomb@med.unc.edu
      • Principal Investigator: Jorge Oldan, MD
      • Sub-Investigator: Yueh Lee, MD, PhD
      • Sub-Investigator: Kristen Olinger, MD

Participation Criteria

Eligibility Criteria

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

Description

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

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

What is the study measuring?

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]

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Radiological Society of North America
• Investigators: Principal Investigator: Jorge Oldan, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): June 28, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: LCCC2221; 22-1677 (Other Identifier: UNC Chapel Hill IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with the University of North Carolina (UNC).
• IPD Sharing Time Frame: 9 to 36 months following publication
• IPD Sharing Access Criteria: The investigator who proposes to use the data has approval from an IRB, IEC, or REB, as applicable, and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No