Clinical trial NCT06086704: Study of 18F-FFNP Breast PET/MRI
Official title: Phase II Study of 18F-FFNP Breast PET/MRI in the Assessment of Early Response of Breast Cancer to Presurgical Endocrine Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: PR+
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-10-17
Enrollment: 53
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Window of Opportunity
Primary purpose: DIAGNOSTIC

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 endocrine therapy and to determine the quantitative reliability of 18F-FFNP breast PET/MRI in patients with newly diagnosed PR+ primary breast cancer.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage change in 18F-FFNP uptake between baseline and follow-up PET/MRI scans
timeFrame: up to 4 weeks on study and up to 7 weeks on study
measure: Percentage change in tumor Ki67 proliferation score, as a surrogate measure of endocrine sensitivity
timeFrame: up to 4 weeks on study and up to 7 weeks on study
Secondary outcomes:
measure: Qualitative Analysis of 18F-FFNP uptake
timeFrame: 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
measure: Intra- and Inter-Observer Variability of Quantitative Assessment of Tumor 18F-FFNP uptake
timeFrame: 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
measure: Quantitative Assessment of Tumor 18F-FFNP: Standardized Uptake Values (SUV)
timeFrame: 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
measure: Test-Retest Variability of Quantitative Assessment of Tumor 18F-FFNP uptake
timeFrame: 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
measure: NCIC Adverse Events Version 5.0 Frequency Tables
timeFrame: up to 7 weeks
Other outcomes:
measure: Summary of Parent and Metabolite Fractions of 18F-FFNP over the course of the scan
timeFrame: imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1
measure: Statistical Correlation between tumor 18F-FFNP uptake with serum progesterone, estradiol, and corticosteroid binding globulin levels
timeFrame: imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1
measure: Statistical correlation between 18F-FFNP breast PET/MRI parameters and changes in PR immunohistochemistry in therapy responders and non-responders
timeFrame: 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
measure: Statistical correlation between tumor 18F-FFNP uptake with disease recurrence
timeFrame: up to 5 years (long term follow up)
measure: Statistical determination of whether MRI parameters improve the predictive value of FFNP PET alone
timeFrame: up to 5 years (long term follow up)
Locations:
city: Madison
country: United States
facility: UW Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: UW Carbone Cancer Center
name: Amy M Fowler, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: