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Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03703492
Recruitment Status : Recruiting
First Posted : October 12, 2018
Last Update Posted : January 30, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Study Description
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Brief Summary:
This prospective, one-arm study which will enroll participants with biopsy-proven DCIS scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Eligible participants will be consented for participation in the research study which includes a directed breast PET/MRI with 18F-FES. 18F-FES uptake of the known malignancy will be measured on the PET/MRI examination using standardized uptake values (SUV) and tumor-to-normal tissue ratios.

Condition or disease Intervention/treatment Phase
Breast Cancer Ductal Carcinoma in Situ - Category Drug: (18F)FES Drug: Gadobenate dimeglumine Phase 2

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 determine the technical feasibility of simultaneous breast DCE MRI with 18F-FES PET for measuring estrogen receptor (ER) in patients with ductal carcinoma in situ (DCIS) and identifying patients with low-risk of disease recurrence. The hypothesis is that quantitative 18F-FES uptake parameters from PET/MRI will correlate well with the ER immunohistochemistry score and with low-risk recurrence scores.

Primary Objective 1) To compare quantitative 18F-FES uptake of biopsy-proven DCIS measured using PET/MRI with ER protein levels determined by immunohistochemistry.

Secondary Objectives

  1. To determine the optimal cut-point 18F-FES uptake value for distinguishing between ER+ and ER-negative DCIS
  2. To determine the test-retest reproducibility of quantitative assessment of tumor 18F-FES uptake
  3. To determine the optimal cut-point 18F-FES uptake value for distinguishing between low-risk DCIS and intermediate/high-risk DCIS
  4. To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100)
  5. To measure the upgrade rate to invasive cancer at surgical excision
  6. To correlate tumor 18F-FES uptake with serum estradiol and sex hormone binding globulin levels.

Exploratory Objective

1) To correlate tumor cell density with 18F-FES uptake on PET/MRI

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a prospective, one-arm, observational study which will enroll participants with biopsy-proven DCIS scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Positron Emission Tomography/Magnetic Resonance Imaging of Estrogen Receptor Expression n Non-Invasive Breast Cancer
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Research Arm
Directed breast PET/MRI with 18F-FES; 18F-FES uptake of the known malignancy to be measured on the PET/MRI examination
 Drug: (18F)FES
18F-FES is an investigational new drug which will be used for this study. For complete information, please refer to the Investigator's Brochure: "[18F]Fluoroestradiol: An investigational positron emission tomography (PET) radiopharmaceutical for injection, intended for use as an in vivo diagnostic for imaging estrogen receptors in tumors
Other Names:
  • 11.2 16α-[18F]-fluoro-17β-estradiol
  • FES

Drug: Gadobenate dimeglumine
Gadolinium-based intravenous contrast agent used for the MRI portion of this study
Other Name: MultiHance


Outcome Measures
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Primary Outcome Measures :
  1. 18F-FES uptake in DCIS [ Time Frame: 1 day ]
    18F-FES uptake of biopsy-proven DCIS measured using PET/MRI will be reported in Standardized Uptake Values (SUV).


Secondary Outcome Measures :
  1. Prognostic risk categories determined using Van Nuys Prognostic index, the MSKCC nomogram [ Time Frame: 2 months ]

    ROC curve analysis will be performed to determine the optimal cut-point for 18F-FES SUVmax to distinguish low-risk DCIS and intermediate/high-risk DCIS. Risk categories will be determined using the Van Nuys Prognostic Index, the Memorial Sloan-Kettering Cancer Center Nomogram, and the research-based Oncotype DX DCIS score. Sensitivity and specificity will be determined with two-sided 95% confidence intervals. The AUCs 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 18F-FES uptake value with the maximum sensitivity and specificity.

    This analysis will be done separately for each risk assessment model.


  2. Research-based Oncotype DX DCIS scores [ Time Frame: 12 months ]
    To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100), scatter plots of continuous quantitative 18F-FES uptake (SUVmax) on the y-axis and research-based Oncotype DX DCIS scores (unitless) on the x-axis will be created to explore the distribution of the measurements. Pearson's or Spearman's rank correlation will be used to evaluate the association between quantitative 18F-FES uptake and research-based Oncotype DX DCIS score. The correlation coefficient (rho) and 95% confidence interval will be reported.

  3. Upgrade Rate to Invasive Cancer at Surgical Excision. [ Time Frame: 2 months ]
    This percentage will be calculated by dividing the number of patients with invasive breast cancer diagnosed at the time of surgical excision by the number of patients with percutaneous biopsy-proven DCIS in the study.

  4. Serum Estradiol Levels [ Time Frame: 1 day ]
    A correlation analysis of serum estradiol levels will be performed using Pearson's or Spearman's rank correlation. Scatter plots, correlation coefficients (rho) and 95% confidence intervals will be reported.

  5. Serum Sex Hormone Binding Globulin Levels [ Time Frame: 1 day ]
    A correlation analysis of sex hormone binding globulin levels will be performed using Pearson's or Spearman's rank correlation. Scatter plots, correlation coefficients (rho) and 95% confidence intervals will be reported.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of biopsy-proven DCIS without invasion or microinvasion measuring at least 1.0 cm in diameter by any imaging modality
  • 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
  • Surgery, radiation, neoadjuvant chemo/endocrine therapy for the current malignancy prior to study enrollment
  • Participants currently taking or have taken an ER-blocking medication (e.g. tamoxifen, raloxifene) within 6 weeks prior to study enrollment
  • Pregnant or lactating women
  • Participant with intolerance or contraindications for MRI or gadolinium-based contrast agents
  • Participant girth exceeds the bore of the MRI/PET scanner
  • Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FES
  • Participants in liver failure as judged by the patient's physician, due to the hepatobiliary clearance of 18F-FES

  • 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 participant 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 or an alternative plan for transportation (e.g. Uber, taxi, etc.)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03703492


Contacts
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Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53705
Contact: Gemma Gliori    608-262-7269    ggliori@uwhealth.org   
Contact: Suzanne Hanson    (608) 263-7421    shanson@uwhealth.org   
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amy Fowler University of Wisconsin, Madison
More Information
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Additional Information:

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Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT03703492    
Other Study ID Numbers: UW18063
KL2TR000428 ( U.S. NIH Grant/Contract )
NCI-2018-02281 ( Registry Identifier: NCI Trial ID )
2018-0814 ( Other Identifier: Institutional Review Board )
A539300 ( Other Identifier: UW Madison )
SMPH/RADIOLOGY/RADIOLOGY ( Other Identifier: UW Madison )
P30CA014520 ( U.S. NIH Grant/Contract )
Protocol Version 5/11/2022 ( Other Identifier: UW Madison )
First Posted: October 12, 2018    Key Record Dates
Last Update Posted: January 30, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Intraductal, Noninfiltrating
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
 Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Carcinoma In Situ
Estradiol
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs