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

Primary Purpose

Invasive Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
[18F]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Invasive Breast Cancer focused on measuring Invasive Breast Cancer, Metastatic Breast Cancer, PR Positive Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 (N=23) or PR-negative (N=5) 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
  • Participant girth exceeds the bore of the PET/MRI scanner
  • 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

Sites / Locations

  • University of Wisconsin, MadisonRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FFNP PET/MRI

Arm Description

18F-Fluorofuranylnorprogesterone (FFNP) administration for PET/MRI imaging to assess biopsy-proven primary PR+ breast malignancies.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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

Full Information

First Posted
June 30, 2017
Last Updated
September 22, 2023
Sponsor
University of Wisconsin, Madison
Collaborators
National Center for Advancing Translational Sciences (NCATS)
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1. Study Identification

Unique Protocol Identification Number
NCT03212170
Brief Title
FFNP-PET/MR Imaging of Progesterone Receptor Expression in Invasive Breast Cancer
Official Title
[18F]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging of Progesterone Receptor Expression in Invasive Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2017 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Center for Advancing Translational Sciences (NCATS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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, observational 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Breast Cancer
Keywords
Invasive Breast Cancer, Metastatic Breast Cancer, PR Positive Breast Cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FFNP PET/MRI
Arm Type
Experimental
Arm Description
18F-Fluorofuranylnorprogesterone (FFNP) administration for PET/MRI imaging to assess biopsy-proven primary PR+ breast malignancies.
Intervention Type
Drug
Intervention Name(s)
[18F]Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging
Other Intervention Name(s)
FFNP
Intervention Description
18F-Fluorofuranylnorprogesterone (FFNP) PET/MR Imaging tracer
Primary Outcome Measure Information:
Title
FFNP Uptake
Description
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.
Time Frame
Up to 1 day
Secondary Outcome Measure Information:
Title
Test-Retest Reproducibility
Description
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.
Time Frame
Up to 4 weeks
Title
Intra and Inter-Observer Assessment
Description
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.
Time Frame
Up to 4 weeks
Title
Association of tumor FFNP uptake with Oncotype DX score
Description
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.
Time Frame
Up to 4 weeks
Title
Distinguishing between PR Negative and PR Positive Breast Cancer
Description
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
Time Frame
up to 4 weeks

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Only women are being targeted for this research as breast MRI is not utilized for male breast cancer patients which comprises only 1% of all breast cancer cases.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 (N=23) or PR-negative (N=5) 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 Participant girth exceeds the bore of the PET/MRI scanner 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gemma Gliori, MS
Phone
608-262-7269
Email
ggliori@uwhealth.org
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne Hanson, BS
Phone
608-263-7421
Email
shanson@uwhealth.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Fowler, MD, PhD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin, Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gemma Gliori, MS
Phone
608-262-7269
Email
ggliori@uwhealth.org
First Name & Middle Initial & Last Name & Degree
Amy Fowler, MD, PhD
First Name & Middle Initial & Last Name & Degree
Roberta Strigel, MD, MS
First Name & Middle Initial & Last Name & Degree
Aparna Mahajan, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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

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