FES (16α-[18F]-Fluoro-17β-estradiol)-PET: Towards a New Standard to Stage Locally Advanced and Recurrent, Estrogen Receptor Positive (ER+) Breast Cancer? Pilot Study to Compare [18F]FES-PET and [18F]FDG-PET (FORESIGHT)

May 2, 2023 updated by: C. Menke- van der Houven van Oordt, Amsterdam UMC, location VUmc
Accurate staging is of great importance in patients with clinically locally advanced primary breast cancer (LABC, stage III) or locoregional recurrent (LRR) breast cancer for making a correct treatment plan. According to current guidelines, staging is performed with positron emission tomography (PET) using the 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET tracer, combined with diagnostic computed tomography (CT). However, previous studies have shown that this technique (with the current PET tracer) might not be sufficient for accurate staging. Specifically in low grade, estrogen receptor positive (ER+) breast cancer metastases can be missed due to the low metabolic activity, leading to low uptake of [18F]FDG. Therefore, there is a clinical need to improve staging procedures. 16α-[18F]-fluoro-17β-estradiol ([18F]FES), an ER-targeted PET tracer, allows imaging of ER+ tumor lesions regardless of their metabolic activity. Patients with clinically LABC and LRR have a 25-50% risk of distant metastases. Correct identification of distant metastases allows adaptation of the treatment plan to avoid burdensome treatment with surgery, systemic and radiotherapy in order to maintain quality of life. In case of oligometastases, correct identification increases the likelihood for cure with local treatment. In the current study we will compare disease staging with [18F]FES- and [18F]FDG PET in patients with clinically LABC/LRR breast cancer. Objective: To determine whether [18F]FES PET/CT improves staging for women with clinically LABC or LRR, ER+/HER2- breast cancer as compared to standard [18F]FDG PET/CT. Study design: Multicenter prospective study with invasive measurements. Study population: 20 LABC and 20 LRR ER+/HER2- breast cancer patients. Main study parameters/endpoints: To determine the percentage of patients with a correctly changed treatment plan according to information obtained from [18F]FES PET/CT compared to [18F]FDG PET/CT at staging and at 6 months of follow-up; to determine the percentage of metastatic lesions detected and missed with [18F]FES PET/CT compared to [18F]FDG PET/CT (at staging and during follow-up). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will receive an intravenous cannula for tracer injection and blood sampling, causing potentially transient discomfort at the site of the cannula insertion. Tumor biopsy will be performed from an easy accessible lesion and the most frequent complications that can occur are discomfort, bleeding and (local) infection. The risk of complications from a tumor biopsy is considered low: 0.24-1.6% and 0.11-0.48% for major complications and mortality, respectively. Radiation exposure from a [18F]FES PET and [18F]FDG PET scan usually ranges between 4-11 mSv and 7-8 mSv, respectively. Radiation exposure from a diagnostic CT scan ranges between 8-14 mSv. The total radiation burden is considered justifiable when compared to the information that can be obtained from this study, in this patient group with breast cancer. Imaging with [18F]FES PET may improve staging for patients with breast cancer as it may show tumor lesions that could not be identified with [18F]FDG PET, the current standard for staging. If this is the case, the initial treatment goal and intensity can be adjusted which can have beneficial effects for the patient.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Noord- Holland
      • Amsterdam, Noord- Holland, Netherlands
        • VU University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinically LABC (stage III) or LRR breast cancer (all histological types) with ER+, HER2- and low grade according to Bloom Richardson criteria (grade 1-2)
  • Females aged 18 years or older at screening
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
  • Candidates for treatment with curative intent (patients are also allowed for inclusion in the current study if they have undergone recent surgery (<6 weeks) for current breast cancer and require staging because of unexpected stage III disease)
  • In case [18F]FDG PET/CT has already been performed, patients can be included <21 days after this scan
  • Estimated glomerular filtration rate (eGFR) ≥30 ml/min
  • Written and signed informed consent

Exclusion Criteria:

  • History with another cancer within the last 5 years, except non-melanoma skin cancer
  • Undergoing treatment for current breast cancer such as (neo)adjuvant chemotherapy, hormonal therapy (only in case of Tamoxifen), radiotherapy or investigational drug therapy
  • Pregnancy or lactating women
  • Any medical, psychological or social condition that may interfere with the subject's safety and participation in the study, will lead to exclusion from this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: [18F]FES
All patients will receive an additional PET/CT scan: [18F]FES PET/CT scan.
Diagnostic test: 18F-Fluorestradiol PET/CT scan
[18F]FES PET/CT scan will be performed after administration of radioactive labelled estrogen.
Other Names:
  • [18F]FES PET/CT scan

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of patients with a correctly changed treatment plan according to [18F]FES PET/CT compared to [18F]FDG PET/CT.
Time Frame: 2 years
Percentage of patients with a correctly changed treatment plan according to information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT at staging.
2 years
Percentage of metastatic lesions detected with [18F]FES PET/CT compared to [18F]FDG PET/CT.
Time Frame: 2 years
Percentage of metastatic lesions detected with [18F]FES PET/CT compared to [18F]FDG PET/CT at staging.
2 years
Percentage of missed metastases with [18F]FES PET/CT compared to [18F]FDG PET/CT.
Time Frame: 2 years
Percentage of missed metastases with [18F]FES PET/CT compared to [18F]FDG PET/CT (at staging and developed during follow-up).
2 years
Percentage of correct treatment plans as well as diagnostic confidence after 6 months of follow-up based on the added information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT.
Time Frame: 2 years
Percentage of correct treatment plans as well as diagnostic confidence after 6 months of follow-up as determined by the adjudication committee based on the added information obtained with [18F]FES PET/CT compared to [18F]FDG PET/CT.
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
[18F]FES/[18F]FDG uptake related to size of the lesion
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to size of the lesion.
2 years
[18F]FES/[18F]FDG uptake related to location of the lesion.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to location of the lesion.
2 years
[18F]FES/[18F]FDG uptake related to histological subtype.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to histological subtype.
2 years
[18F]FES/[18F]FDG uptake related to grade.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to grade.
2 years
[18F]FES/[18F]FDG uptake related to ER expression level.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to ER expression level.
2 years
[18F]FES/[18F]FDG uptake related to PR expression level.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to PR expression level.
2 years
[18F]FES/[18F]FDG uptake related to HER2 expression level.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to HER2 expression level.
2 years
[18F]FES/[18F]FDG uptake related to Ki67%/mitotic index.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to Ki67%/mitotic index.
2 years
[18F]FES/[18F]FDG uptake related to intensity of ER staining.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to intensity of ER staining.
2 years
[18F]FES/[18F]FDG uptake related to intensity of tumor cell density.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to intensity of tumor cell density.
2 years
[18F]FES/[18F]FDG uptake related to intensity of microvessel density.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to intensity of microvessel density.
2 years
[18F]FES/[18F]FDG uptake related to infiltration of lymphocytes.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to infiltration of lymphocytes.
2 years
[18F]FES/[18F]FDG uptake related to amount of necrosis.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to amount of necrosis.
2 years
[18F]FES/[18F]FDG uptake related to amount of stroma.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to amount of stroma.
2 years
[18F]FES/[18F]FDG uptake related to expression of glucose transporter-1 (GLUT1) in the primary tumor, lymph node and distant metastases.
Time Frame: 2 years
[18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to expression of glucose transporter-1 (GLUT1) in the primary tumor, lymph node and distant metastases.
2 years
Cut off value for [18F]FDG SUV max below which [18F]FES PET/CT adds information for staging.
Time Frame: 2 years
Cut off value for [18F]FDG SUV max below which [18F]FES PET/CT adds information for staging.
2 years
Cut off value for [18F]FDG SUV peak below which [18F]FES PET/CT adds information for staging.
Time Frame: 2 years
Cut off value for [18F]FDG SUV peak below which [18F]FES PET/CT adds information for staging.
2 years
Cut off value for grade below which or above which [18F]FES PET/CT adds information for staging.
Time Frame: 2 years
Cut off value for grade below which or above which, respectively, [18F]FES PET/CT adds information for staging.
2 years
Cut off value for ER expression level below which or above which [18F]FES PET/CT adds information for staging.
Time Frame: 2 years
Cut off value for ER expression level below which or above which [18F]FES PET/CT adds information for staging.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amsterdam UMC, location VUmc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 13, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 29, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 29, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 16, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 3, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 2, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2018.451

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings