Assessment of Functional Status of Estrogen Receptors in Breast Cancer by Positron Emission Tomography

The purpose of this study is to evaluate the uptake of a radioactive tracer 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione (FFNP) uptake, which binds to breast cancer progesterone receptors (PgRs) on a PET/CT scan before and after administration of estradiol for one day (estrogen challenge) to determine if the change in uptake is a predictor of response to endocrine therapy (ET) in patients with hormone-sensitive estrogen receptor positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Estradiol is the most potent of the naturally occurring estrogens, and can be administered to treat menopausal symptoms and also sometimes to treat metastatic breast cancer. The investigators propose to study patients with biopsy-proven newly diagnosed, locally advanced, metastatic, or recurrent breast cancer who are going to be treated with endocrine therapy (ET) (tamoxifen,aromatase inhibitors or fulvestrant as standard of care therapy.

Subjects will undergo a total of two FFNP-PET/CT scans; one before and a second one immediately following the one day estradiol challenge before the start of standard of care ET. The estradiol challenge will consist of administering a total of 6 mg of estradiol orally (three doses of 2 mg each) given at approximately 8 hour intervals and over a 24 hour period.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Estradiol; Drug: 18F-FFNP; Device: CTI/Siemens Biograph 40 PET/CT Scanner; Drug: 18F-FDG

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient must be postmenopausal defined as meeting one or more of the following:

  • Age ≥ 60 years
  • Amenorrheic for at least 12 months
  • Surgically sterile- having undergone bilateral oophorectomy,
  • FSH level in postmenopausal range according to institutional standards (note follicle-stimulating hormone (FSH) laboratory testing must be ordered as standard of care to determine optimal treatment and should not be ordered simply to confirm eligibility to this study)
  • OR Pre-menopausal for whom standard estradiol treatment (ET) is planned with ovarian suppression (imaging on study should be completed prior to start of ovarian suppression)

• Patient must have histological or cytological confirmed breast cancer and fall into one of the following categories:

  • New diagnosis with plans for at least 6 months of neoadjuvant ET or any amount of neoadjuvant ET if surgery is planned as this will be used for response assessment .
  • Patients with newly diagnosed metastatic breast cancer or patient with known metastatic disease who has progressed while on therapy (no washout period is needed if the patient was treated with AIs or chemotherapy, but 2 months washout period is needed if the patient was treated with tamoxifen) who are going to be treated with ET.

• Patient must have any one of the following types of breast cancer (primary or metastatic): ER+/PgR+/HER2- or ER+/PgR-/HER2-.

  • ER+ is defined as Allred score of at least 4 and greater.
  • PgR+ is defined as Allred score of at least 4 and greater.
  • Immunohistochemistry (IHC) is the primary assay methodology for HER2. HER2- refers to HER2 of 0, 1+ by IHC or negative by fluorescence in situ hybridization (FISH)

• Patient must have at least one measurable lesion according to RECIST 1.1 by radiological evaluation (ultrasound, mammography, MRI, CT, PET) or physical examination.

  • Patients with evaluable osseous metastasis that are lytic or mixed lytic-sclerotic are eligible.
  • Patients with hepatic lesions may be eligible provided the location of the lesion is peripheral or not too close to hepatic ducts. Decision on hepatic lesion eligibility will be made by the principal investigator or sub-investigator after careful review of all available imaging to ensure evaluation of the lesion will not be obscured by normal hepatobiliary excretion of 18F-FFNP.
• Patient must be able to understand and willing to sign a written informed consent document.
• Prior chemotherapy or endocrine therapy is allowed
• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or, based on the judgment of the treating medical oncologist, can tolerate imaging and at least 6 months of ET
• The patient should have a life expectancy of > 6 months.

Exclusion Criteria:

• Patient with other invasive malignancies, with the exception of non-melanoma skin cancer or cervical carcinoma in-situ, who had (or have) any evidence of the other cancer present within the last 5 years
• Unable to tolerate up to 60 min of PET imaging per imaging session.
• Patients with non-measurable non-evaluable lesions such as pleural effusion are not eligible to participate.
• Patients with vertebral lesions that, in the opinion of the Principal Investigator and the treating medical oncologist, pose an imminent risk for cord compression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic FFNP-PET/CT Scan; (2) 18F-FFNP-PET/CT scansFirst one prior to estradiol challenge testSecond one immediately following one day of estradiol challenge test; (1) FDG-PET/CT scan at screening; The estradiol challenge test will consist of administering a total of 6 mg of estradiol dosed orally as three 2 mg tablets with each tablet being administered approximately 8 hours apart and within a 24 hour period. This estradiol medication will be provided to the patient by the study.

Drug: Estradiol; Drug: 18F-FFNP; Other Names: 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione; Device: CTI/Siemens Biograph 40 PET/CT Scanner; Will include (1) 18-FDG-PET/CT scan; Will include (2) 18F-FFNP-PET/CT scans; Drug: 18F-FDG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Primary Tumor FFNP Uptake Before and After Estradiol Challenge as Measured by Percent Change in Standardized Uptake Value (SUV)	Completion of second FFNP-PET/CT scan (up to 4 weeks)
Change in Secondary Tumor FFNP Uptake Before and After Estradiol Challenge as Measured by Percent Change in Standardized Uptake Value (SUV)	Completion of second FFNP-PET/CT scan (up to 4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heterogeneity of Tumor FFNP Uptake as Measured by Number of Participants With Heterogenous Response	As measured visually in known lesion by recording presence or absence of uptake with note of any changes between scans	Completion of second FFNP-PET/CT scan (up to 4 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Dehdashti F, Wu N, Ma CX, Naughton MJ, Katzenellenbogen JA, Siegel BA. Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy. Nat Commun. 2021 Feb 2;12(1):733. doi: 10.1038/s41467-020-20814-9.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2015
• Primary Completion (Actual): January 3, 2019
• Study Completion (Actual): January 3, 2019

Study Registration Dates

• First Submitted: May 14, 2015
• First Submitted That Met QC Criteria: May 22, 2015
• First Posted (Estimate): May 27, 2015

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: 201411005; 5R01CA195450-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes