Study of 18F-FFNP Breast PET/MRI

University of Wisconsin (UW)

Status and phase: Enrolling; Phase 2

Conditions: Breast Cancer

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06086704

1R01CA272571-01 (U.S. NIH Grant/Contract)

2023-1114

Protocol Version 7/30/2024 (Other Identifier)

SMPH/RADIOLOGY/RADIOLOGY (Other Identifier)

UW23020 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 53 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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53 participants in 3 patient groups

Group 1: Metabolite Analysis

Experimental group

Description:

participants will undergo venous blood sampling during the PET/MRI scan

Treatment:

Device: Positron Emissions Tomography / Magnetic Resonance Imaging

Drug: FDA-approved gadolinium-based intravenous contrast agent

Drug: 18F-fluorofuranylnorprogesterone

Other: Blood Sampling

Group 2: Pre-surgical Treatment

Experimental group

Description:

participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole

Treatment:

Drug: Anastrozole

Device: Positron Emissions Tomography / Magnetic Resonance Imaging

Drug: FDA-approved gadolinium-based intravenous contrast agent

Drug: 18F-fluorofuranylnorprogesterone

Group 3: Test-Retest

Experimental group

Description:

participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability

Treatment:

Device: Positron Emissions Tomography / Magnetic Resonance Imaging

Drug: FDA-approved gadolinium-based intravenous contrast agent

Drug: 18F-fluorofuranylnorprogesterone