Study of 18F-FFNP Breast PET/MRI

Phase II Study of 18F-FFNP Breast PET/MRI in the Assessment of Early Response of Breast Cancer to Presurgical Endocrine Therapy

This clinical trial will investigate an estrogen-regulated parameter as an early measure of endocrine therapy response: progesterone receptor (PR) protein with a progestin-based radioligand, 18F-fluorofuranylnorprogesterone (18F-FFNP). The overall purpose of this research is to test the efficacy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy and to determine the quantitative reliability of 18F-FFNP breast PET/MRI in patients with newly diagnosed PR+ primary breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 18F-fluorofuranylnorprogesterone; Device: Positron Emissions Tomography / Magnetic Resonance Imaging; Other: Blood Sampling; Drug: Anastrozole; Drug: FDA-approved gadolinium-based intravenous contrast agent

Detailed Description

Primary Objective

• Determine the diagnostic accuracy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy.

Secondary Objectives

• Determine the repeatability of quantitative assessment of tumor 18F-FFNP uptake.
• Determine the intra- and inter-observer variability of quantitative assessment of tumor 18F-FFNP uptake.
• Assess the safety and tolerability of 18F-FFNP.

Exploratory Objectives

• Define the parent and metabolite fractions of 18F-FFNP over the time course of the scan.
• Assess the association between tumor 18F-FFNP uptake with serum progesterone, estradiol, and corticosteroid binding globulin levels.
• Compare changes in 18F-FFNP breast PET/MRI parameters with changes in PR immunohistochemistry in therapy responders and non-responders.
• Assess the association between tumor 18F-FFNP uptake with disease recurrence.
• Determine whether MRI parameters improve the predictive value of FFNP PET alone.

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cancer Connect; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • UW Carbone Cancer Center
      • Sub-Investigator: Scott B Perlman, MD
      • Sub-Investigator: Roberta M Strigel, MD, MS
      • Sub-Investigator: Kari B Wisinski, MD
      • Sub-Investigator: Lee G Wilke, MD
      • Sub-Investigator: Lonie R Salkowski, MD, MS, PhD
      • Sub-Investigator: Aparna M Mahajan, MD
      • Sub-Investigator: Stephanie M McGregor, MD, PhD
      • Sub-Investigator: Emmanuel Sampene, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postmenopausal status defined by either

  • prior bilateral oophorectomy
  • age greater than or equal to 60 years of age
  • age less than 60 years of age and amenorrheic for 12 or more months in the absence of prior chemotherapy, tamoxifen, toremifene or ovarian suppression and FSH and estradiol in the postmenopausal range per local normal range (Group 2 only)
• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in diameter by any imaging modality. Malignancy may be located within the breast, axilla (e.g. metastatic axillary lymph node), or both the breast and axilla
• Biopsy-proven PR-positive invasive breast cancer
• Definitive surgical excision of the primary tumor planned without neoadjuvant therapy; defined as therapy (chemotherapy, targeted therapy, radiation therapy or endocrine therapy) given to decrease the size of the tumor prior to planned surgery. (Group 2 only)

Exclusion Criteria:

• Inability or unwillingness to provide informed consent to the study
• HER2-positive breast cancer, as defined by immunohistochemical staining 3+ OR positive by in situ hybridization (Group 2 only)
• PR and Ki67 IHC slides or FFPE tissue blocks from clinical breast biopsy not available
• Patients who have completed neoadjuvant chemotherapy, endocrine therapy, targeted therapy, surgical resection, or radiation for the current biopsy-proven malignancy (Group 2 only)
• Patients who are planning to undergo anastrozole as standard of care neoadjuvant therapy
• Patients who are currently taking aromatase inhibitors or ER antagonists (tamoxifen, raloxifene)
• Patients with breast expanders
• Patients who are pregnant or lactating
• Patients with clinical contraindication for use of aromatase inhibitors (AI) while on study as determined by investigator (Group 2 only)
• Patients with a contraindication to gadolinium-based contrast agents, including allergy or impaired renal function (per UW Health Guidelines)
• Patients with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FFNP
• Patients with history of allergic reaction to anastrozole (Group 2 only)
• Patients in liver failure as judged by the patient's physician
• Patients with standard contraindications to MRI (per UW Health Guidelines)

• Patients requiring conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:

  • The patient has their own prescription for the medication
  • The informed consent process is conducted prior to the self-administration of the medication.
  • The patient comes to the research visit with a driver.
• Patients unable to lie prone for 45 minutes for imaging

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Metabolite Analysis; participants will undergo venous blood sampling during the PET/MRI scan	Drug: 18F-fluorofuranylnorprogesterone; 18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.; Other Names: FFNP; Device: Positron Emissions Tomography / Magnetic Resonance Imaging; Breast specific PET/MRI data will be acquired using a 3T simultaneous PET/MRI scanner (Signa PET/MR, GE Healthcare); Other Names: PET/MRI; Other: Blood Sampling; Venous blood samples will be collected at multiple timepoints (e.g., 5, 10, 20, 30, and 45 min after 18F-FFNP injection to determine parent and metabolite fractions; Drug: FDA-approved gadolinium-based intravenous contrast agent; FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study; Other Names: gadopiclenol; gadobenate dimuglumine
Experimental: Group 2: Pre-surgical Treatment; participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole	Drug: 18F-fluorofuranylnorprogesterone; 18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.; Other Names: FFNP; Device: Positron Emissions Tomography / Magnetic Resonance Imaging; Breast specific PET/MRI data will be acquired using a 3T simultaneous PET/MRI scanner (Signa PET/MR, GE Healthcare); Other Names: PET/MRI; Drug: Anastrozole; hormone based chemotherapy that reduces estrogen, 1 mg anastrozole once daily by mouth for a minimum of 14 days; Drug: FDA-approved gadolinium-based intravenous contrast agent; FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study; Other Names: gadopiclenol; gadobenate dimuglumine
Experimental: Group 3: Test-Retest; participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability	Drug: 18F-fluorofuranylnorprogesterone; 18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.; Other Names: FFNP; Device: Positron Emissions Tomography / Magnetic Resonance Imaging; Breast specific PET/MRI data will be acquired using a 3T simultaneous PET/MRI scanner (Signa PET/MR, GE Healthcare); Other Names: PET/MRI; Drug: FDA-approved gadolinium-based intravenous contrast agent; FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study; Other Names: gadopiclenol; gadobenate dimuglumine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in 18F-FFNP uptake between baseline and follow-up PET/MRI scans	Tumor uptake values of 18F-FFNP will be obtained from the attenuation corrected PET component of the simultaneous breast 18F-FFNP PET/MRI research scan according to the procedures detailed in the imaging manual and the FDA IND.	up to 4 weeks on study and up to 7 weeks on study
Percentage change in tumor Ki67 proliferation score, as a surrogate measure of endocrine sensitivity	Baseline Ki67 proliferation immunohistochemistry score will be obtained from the existing clinical standard-of-care breast biopsy. Post-treatment K67 proliferation immunohistochemistry score will be obtained from the surgical specimen after excision. Treatment response is defined as a reduction in Ki67 score of greater than or equal to 60 percent. Treatment nonresponse is defined as a reduction of less than 60 percent.	up to 4 weeks on study and up to 7 weeks on study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative Analysis of 18F-FFNP uptake	18F-FFNP uptake will be visually evaluated qualitatively with the following grading scale: no uptake (tumor < background), minimal uptake (tumor = background), mild (tumor slightly > background), moderate uptake (tumor >> background), and intense uptake (tumor >>> background). Tumor uptake will also be dichotomized as increased (mild, moderate, or intense uptake) or absent (no uptake, minimal).	imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
Intra- and Inter-Observer Variability of Quantitative Assessment of Tumor 18F-FFNP uptake	For the test-retest portion of the clinical trial, the mixed effects model framework will be utilized to determine the intra- and interobserver variability of quantitative assessment of tumor 18F-FFNP uptake via a parametric bootstrapping approach.	imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
Quantitative Assessment of Tumor 18F-FFNP: Standardized Uptake Values (SUV)	Differences in repeatability of the different SUV measures (SUVmax, SUVpeak, and SUVmean) and their respective methods of normalization will be assessed by comparing the variances of the relative test-retest differences, using the Pitnam-Morgan test for correlated variances.	imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
Test-Retest Variability of Quantitative Assessment of Tumor 18F-FFNP uptake	For the test-retest portion of the clinical trial, the mixed effects model framework will be utilized to determine the test-retest variability of quantitative assessment of tumor 18F-FFNP uptake via a parametric bootstrapping approach.	imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
NCIC Adverse Events Version 5.0 Frequency Tables	Safety and tolerability of 18F-FFNP by NCIC Adverse Events Version 5.0 will be assessed by frequency tables and possible relationship to study drug as assessed by the investigators.	up to 7 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Parent and Metabolite Fractions of 18F-FFNP over the course of the scan	Median and interquartile ranges will be calculated for metabolized and unmetabolized (parent) 18F-FFNP obtained from subjects undergoing venous blood sampling in the metabolite study and plotted against time.	imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1
Statistical correlation between 18F-FFNP breast PET/MRI parameters and changes in PR immunohistochemistry in therapy responders and non-responders	An ANCOVA model, which will include treatment as a fixed effect and the corresponding baseline value as a covariate, and a paired t-test will be utilized to compare the change in tumor 18F-FFNP update after window treatment with change in PR immunostaining from the biopsy to surgical specimen. Means and standard errors will be presented. Least-squares means and 95% CI will be reported. Furthermore, correlation analyses will be performed to describe these associations.	imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1, up to 4 weeks and up to 7 weeks for Group 2, and up to 4 weeks and up to 6 weeks for Group 3
Statistical correlation between tumor 18F-FFNP uptake with disease recurrence	If there is sufficient follow-up data for disease recurrence, the Kaplan-Meier method will be used to analyze time to disease recurrence, defined as date of imaging day until disease recurrence. Patients who do not experience disease recurrence will be censored at the date of last available follow-up. A Cox proportional hazards model will be used to evaluate the association of tumor 18F-FFNP uptake with time to disease recurrence. If there is insufficient follow-up data, descriptive statistics will be used to summarize tumor 18F-FFNP uptake for those patients with disease recurrence	up to 5 years (long term follow up)
Statistical determination of whether MRI parameters improve the predictive value of FFNP PET alone	The investigators will explore whether adding MRI parameters improves the AUC of 18F-FFNP PET alone. Regression models will be performed on the following parameters: quantitative tumor perfusion (signal enhancement ratio, functional tumor volume), quantitative tumor diffusion (apparent diffusion coefficient), qualitative morphologic phenotype (categories I, II, III, IV), and qualitative background parenchymal enhancement (categories are minimal, mild, moderate, marked).	up to 5 years (long term follow up)
Statistical Correlation between tumor 18F-FFNP uptake with serum progesterone, 17-OH progesterone, estradiol, and corticosteroid binding globulin levels	Pearson's or Rank correlation analysis will be performed to assess the association between tumor 18F-FFNP uptake with serum progesterone, estradiol, and corticosteroid binding globulin levels. Scatter plots, correlation coefficients (rho), 95% confidence intervals, and p values will be reported.	imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Amy M Fowler, MD, PHD, UW Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 17, 2023

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PR+
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Azoles; Tomography; Diagnostic Imaging; Nitriles; Triazoles; Anastrozole; Magnetic Resonance Imaging; Blood Specimen Collection; gadopiclenol
• Other Study ID Numbers: 2023-1114; SMPH/RADIOLOGY/RADIOLOGY (Other Identifier: UW Madison); UW23020 (Other Identifier: UWCCC OnCore ID); 1R01CA272571-01 (U.S. NIH Grant/Contract); Protocol Version 7/30/2024 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No