FFNP-PET/MR Imaging of Progesterone Receptor Expression in Invasive Breast Cancer

Invasive Breast Cancer Clinical Trial

Official title:

[18F]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging of Progesterone Receptor Expression in Invasive Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03212170
• Other study ID #: 2017-0533
• Secondary ID: UW17034 / UW2300
• Status: Recruiting
• Phase: Phase 2
• Start date: December 13, 2017
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: University of Wisconsin, Madison
• Contact: Gemma Gliori, MS
• Phone: 608-262-7269
• Email: ggliori[@]uwhealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this research is to test the accuracy of PET/MRI imaging with 18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression in patients with invasive breast cancer. The hypothesis is that FFNP SUVmax from PET/MRI will correlate well against the semi-quantitative PR immunohistochemistry score.

Description:

Integrated whole-body magnetic resonance imaging (MRI)-positron emission tomography (PET) scanners have recently been introduced for clinical use. This technology combines the anatomic and perfusion data obtained with dynamic contrast enhanced (DCE) MRI with functional imaging data obtained from PET. For breast imaging, the combination of MRI and PET has important potential to improve diagnostic accuracy and provide molecular characterization of breast cancer. The overall purpose of this research is to test the accuracy of PET/MRI imaging with 18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression in patients with invasive breast cancer. This is a prospective, one-arm, study which will enroll patients with newly diagnosed breast cancer scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Participation in this research study includes a directed breast PET/MRI with the investigational radiopharmaceutical, FFNP. FFNP uptake of the known, biopsy-proven malignancy will be measured on the PET/MRI examinations using standardized uptake values (SUV) and tumor-to-normal tissue ratios.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women 18 years of age or older
• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in diameter by any imaging modality
• Biopsy-proven PR-positive or PR-negative invasive breast cancer
• Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease

Exclusion Criteria:

• Inability or unwillingness to provide informed consent to the study
• Participants currently undergoing neoadjuvant chemotherapy/endocrine therapy or those who have received chemotherapy/endocrine therapy within 6 months prior to the MRI
• Participants who have had neoadjuvant chemotherapy/endocrine therapy, surgical intervention, or radiation for the current biopsy-proven malignancy
• Participants with breast expanders
• Participants who are or might be pregnant or lactating
• Participants with a contraindication to gadolinium based contrast agents, including allergy or impaired renal function (per University of Wisconsin Health Guidelines)
• Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP
• Participants in liver failure as judged by the patient's physician
• Participants with standard contraindications to MRI, including claustrophobia and metallic implants incompatible with MRI
• Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be

allowed to participate as long as the following criteria are met:

• The subject has their own prescription for the medication
• The informed consent process is conducted prior to the self-administration of this medication
• They come to the research visit with a driver
• Participants unable to lie prone for 30 minutes for imaging

Related Conditions & MeSH terms

• Breast Neoplasms
• Invasive Breast Cancer

Intervention

Drug:
• [18F]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging
18F-Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging tracer

Locations

Country	Name	City	State
United States	University of Wisconsin, Madison	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FFNP Uptake	To compare FFNP uptake of biopsy-proven primary PR+ breast malignancies measured using PET/MRI with the reference standard of PR immunohistochemistry (IHC) using a semi-quantitative score obtained by using the Allred score (0-8; the higher the score, the more receptors were found). The correlation of the two measures will be evaluated with Pearson's correlation coefficient. The null hypothesis is H0: p0=0.50 and the alternative hypothesis is H1: p1 =0.75.	Up to 1 day
Secondary	Test-Retest Reproducibility	Tumor uptake of FFNP and the ability to reproduce this measure, will be quantified in the 5 subjects who elect to undergo a second imaging session, using summary statistics of tumor FFNP uptake for each reading for PET/MRI. The analysis will be done separately for each reader.	Up to 4 weeks
Secondary	Intra and Inter-Observer Assessment	The variability of observer assessment of tumor FFNP uptake will be measured. The intra- and inter-reader agreement of SUV values for tumor FFNP uptake will be analyzed with Bland-Altman plots and 95% limits of agreement. Analyses will be conducted on a per-lesion basis, and repeat tumors within the same patient will be assumed to be independent.	Up to 4 weeks
Secondary	Association of tumor FFNP uptake with Oncotype DX score	Estimate the association of tumor FFNP uptake (continuous SUVmax) with research-based Oncotype DX scores (0-100). The risk score (0-100) is generated from expression levels of sixteen cancer related genes and five reference genes. Scores are further categorized as low-risk (0-17), intermediate-risk (18-30), and high-risk (31-100). Pearson's or Spearman's rank correlation will be used to evaluate the association between FFNP uptake and research-based Oncotype DX score. The correlation coefficient (rho) and 95% confidence interval will be reported.	Up to 4 weeks
Secondary	Distinguishing between PR Negative and PR Positive Breast Cancer	To evaluate the optimal cut-point of FFNP uptake for distinguishing between PR-negative and PR-positive invasive breast cancer. Receiver operating characteristic (ROC) curve analysis will be performed to determine the optimal cut-point for FFNP uptake to distinguish PR-positive from PR-negative invasive breast cancer, as defined by the clinical pathology report. The area under the curve for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the FFNP uptake value with the maximum sensitivity and specificity. The analysis will be done separately for each reader	up to 4 weeks