Study of 18F-FFNP Breast PET/MRI

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06086704
• Other study ID #: 2023-1114
• Secondary ID: Protocol Version
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: January 2030

Study information

• Verified date: May 2024
• Source: University of Wisconsin, Madison
• Contact: Cancer Connect
• Phone: 800-622-8922
• Email: clinicaltrials[@]cancer.wisc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 ER+/PR+/HER2- primary breast cancer.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: January 2030
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in diameter by any imaging modality

• Biopsy-proven ER-positive, PR-positive, HER2-negative 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

• 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 whose girth exceeds the bore of the PET/MRI scanner

• 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

• 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 18F-fluorofuranylnorprogesterone
18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.

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)

Drug:
• Anastrozole
hormone based chemotherapy that reduces estrogen, 1 mg anastrozole once daily by mouth for a minimum of 14 days

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:
• Gadobenate dimeglumine
FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study

Locations

Country	Name	City	State
United States	UW Carbone Cancer Center	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Statistical Correlation between tumor 18F-FFNP uptake with serum 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
Other	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
Other	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)
Other	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)
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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