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.
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
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
53
18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.
Breast specific PET/MRI data will be acquired using a 3T simultaneous PET/MRI scanner (Signa PET/MR, GE Healthcare)
hormone based chemotherapy that reduces estrogen, 1 mg anastrozole once daily by mouth for a minimum of 14 days
UW Carbone Cancer Center
Madison, Wisconsin, United States
RECRUITINGPercentage 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.
Time frame: 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.
Time frame: up to 4 weeks on study and up to 7 weeks on study
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).
Time frame: 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.
Time frame: 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
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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
FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study
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.
Time frame: 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.
Time frame: 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.
Time frame: up to 7 weeks