Study of 18F-FFNP Breast PET/MRI

Phase 2

Recruiting

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

• Registration Number: NCT06086704
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

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 endo...

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.
...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2023-10-11
• Study First Submitted QC: 2023-10-11
• Study First Posted: 2023-10-17
• Study Start: 2024-09-25
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-26
• Primary Completion: 2027-01
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 53

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

• Biopsy-proven PR-positive invasive breast cancer

• Breast MRI planned or performed before surgery

• 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.

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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

• 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 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

• Patients taking hormone replacement therapy or over-the-counter products/supplements/herbal preparation with potential estrogenic effects who are unwilling to discontinue these agents during the timeframe of the study until surgery.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Metabolite Analysis	18F-fluorofuranylnorprogesterone	participants will undergo venous blood sampling during the PET/MRI scan
Group 1: Metabolite Analysis	Positron Emissions Tomography / Magnetic Resonance Imaging	participants will undergo venous blood sampling during the PET/MRI scan
Group 1: Metabolite Analysis	Blood Sampling	participants will undergo venous blood sampling during the PET/MRI scan
Group 1: Metabolite Analysis	FDA-approved gadolinium-based intravenous contrast agent	participants will undergo venous blood sampling during the PET/MRI scan
Group 2: Pre-surgical Treatment	18F-fluorofuranylnorprogesterone	participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole
Group 2: Pre-surgical Treatment	Positron Emissions Tomography / Magnetic Resonance Imaging	participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole
Group 2: Pre-surgical Treatment	Anastrozole	participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole
Group 2: Pre-surgical Treatment	FDA-approved gadolinium-based intravenous contrast agent	participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole
Group 3: Test-Retest	18F-fluorofuranylnorprogesterone	participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability
Group 3: Test-Retest	Positron Emissions Tomography / Magnetic Resonance Imaging	participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability
Group 3: Test-Retest	FDA-approved gadolinium-based intravenous contrast agent	participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability

Primary Outcome Measures

Name	Time	Method
Percentage change in 18F-FFNP uptake between baseline and follow-up PET/MRI scans	up to 4 weeks on study and up to 7 weeks on study	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.
Percentage change in tumor Ki67 proliferation score, as a surrogate measure of endocrine sensitivity	up to 4 weeks on study and up to 7 weeks on study	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.; ...

Secondary Outcome Measures

Name	Time	Method
Intra- and Inter-Observer Variability of Quantitative Assessment of Tumor 18F-FFNP uptake	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	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.
Quantitative Assessment of Tumor 18F-FFNP: Standardized Uptake Values (SUV)	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	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.
Test-Retest Variability of Quantitative Assessment of Tumor 18F-FFNP uptake	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	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.
Qualitative Analysis of 18F-FFNP uptake	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	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 int...
NCIC Adverse Events Version 5.0 Frequency Tables	up to 7 weeks	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.

Trial Locations

Locations (1)

UW Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States