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AzTrials

Breast CancerFORESIGHTNCT03726931

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

A study testing 18F-Fluorestradiol PET/CT scan in people with Breast Cancer, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
18F-Fluorestradiol PET/CT scan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteNetherlands
Study dates
13 Nov 2018to 29 Jan 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • VU University Medical Center

    Amsterdam, North Holland

Other trials in Netherlands

About this study

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.

Conditions
Breast Cancer
Being tested
18F-Fluorestradiol PET/CT scan
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 18F-Fluorestradiol PET/CT scanDiagnostic test

    Also called [18F]FES PET/CT scan

    [18F]FES PET/CT scan will be performed after administration of radioactive labelled estrogen.

Study groups in NCT03726931
Study groupRoleWhat they receive
[18F]FESExperimentalAll patients will receive an additional PET/CT scan: [18F]FES PET/CT scan.
Receives: Diagnostic Test: 18F-Fluorestradiol PET/CT scan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients with a correctly changed treatment plan according to [18F]FES PET/CT compared to [18F]FDG PET/CT.

    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.

    Measured: 2 years

  2. Percentage of metastatic lesions detected with [18F]FES PET/CT compared to [18F]FDG PET/CT.

    Percentage of metastatic lesions detected with [18F]FES PET/CT compared to [18F]FDG PET/CT at staging.

    Measured: 2 years

  3. Percentage of missed metastases with [18F]FES PET/CT compared to [18F]FDG PET/CT.

    Percentage of missed metastases with [18F]FES PET/CT compared to [18F]FDG PET/CT (at staging and developed during follow-up).

    Measured: 2 years

  4. 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.

    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.

    Measured: 2 years

Secondary outcomes (19)

  1. [18F]FES/[18F]FDG uptake related to size of the lesion

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to size of the lesion.

    Measured: 2 years

  2. [18F]FES/[18F]FDG uptake related to location of the lesion.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to location of the lesion.

    Measured: 2 years

  3. [18F]FES/[18F]FDG uptake related to histological subtype.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to histological subtype.

    Measured: 2 years

  4. [18F]FES/[18F]FDG uptake related to grade.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to grade.

    Measured: 2 years

  5. [18F]FES/[18F]FDG uptake related to ER expression level.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to ER expression level.

    Measured: 2 years

  6. [18F]FES/[18F]FDG uptake related to PR expression level.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to PR expression level.

    Measured: 2 years

  7. [18F]FES/[18F]FDG uptake related to HER2 expression level.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to HER2 expression level.

    Measured: 2 years

  8. [18F]FES/[18F]FDG uptake related to Ki67%/mitotic index.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to Ki67%/mitotic index.

    Measured: 2 years

  9. [18F]FES/[18F]FDG uptake related to intensity of ER staining.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to intensity of ER staining.

    Measured: 2 years

  10. [18F]FES/[18F]FDG uptake related to intensity of tumor cell density.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to intensity of tumor cell density.

    Measured: 2 years

  11. [18F]FES/[18F]FDG uptake related to intensity of microvessel density.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to intensity of microvessel density.

    Measured: 2 years

  12. [18F]FES/[18F]FDG uptake related to infiltration of lymphocytes.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to infiltration of lymphocytes.

    Measured: 2 years

  13. [18F]FES/[18F]FDG uptake related to amount of necrosis.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to amount of necrosis.

    Measured: 2 years

  14. [18F]FES/[18F]FDG uptake related to amount of stroma.

    [18F]FES/[18F]FDG uptake in the primary tumor, lymph node and distant metastases will be related to amount of stroma.

    Measured: 2 years

  15. [18F]FES/[18F]FDG uptake related to expression of glucose transporter-1 (GLUT1) in the primary tumor, lymph node and distant metastases.

    [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.

    Measured: 2 years

  16. Cut off value for [18F]FDG SUV max below which [18F]FES PET/CT adds information for staging.

    Cut off value for [18F]FDG SUV max below which [18F]FES PET/CT adds information for staging.

    Measured: 2 years

  17. Cut off value for [18F]FDG SUV peak below which [18F]FES PET/CT adds information for staging.

    Cut off value for [18F]FDG SUV peak below which [18F]FES PET/CT adds information for staging.

    Measured: 2 years

  18. Cut off value for grade below which or above which [18F]FES PET/CT adds information for staging.

    Cut off value for grade below which or above which, respectively, [18F]FES PET/CT adds information for staging.

    Measured: 2 years

  19. Cut off value for ER expression level below which or above which [18F]FES PET/CT adds information for staging.

    Cut off value for ER expression level below which or above which [18F]FES PET/CT adds information for staging.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2018
  2. Study start13 Nov 2018
  3. Primary completion29 Jan 2023
  4. Study completion29 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Model description
In this multicenter observational study with invasive measurements, patients with clinically ER+/HER2- LABC and LRR breast cancer will be included. All patients will undergo the current 'standard' diagnostic procedures including a histological biopsy of the primary tumor, cytology of axillary lymph nodes and imaging procedures with mammography, ultrasound of breast and axilla, magnetic resonance imaging (MRI) breast and whole body \[18F\]FDG PET combined with diagnostic chest/abdominal CT. In addition, all patients will undergo the 'experimental' imaging procedure with \[18F\]FES PET/CT. After evaluation of the obtained scans (independently for both scans), an 'experimental histological biopsy' of a lymph node metastasis will be obtained and clinically relevant \[18F\]FDG+ and/or \[18F\]FES+ lesions and/or suspicious lesions on CT will be biopsied according to standard clinical practice for pathological analyses.
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03726931
Sponsor's protocol ID
2018.451
Acronym
FORESIGHT
Status last verified
May 2023
First submitted
16 Oct 2018
Last updated
3 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Knip JJ, Iqbal R, Bonjer EC, Mammatas LH, van Zweeden AA, Perin P, Teunissen JJM, Diepenhorst GMP, Schijf LJ, Bakker SD, Schoenmakers N, van der Velde S, Barbe E, Duvivier K, Konings IR, Zwezerijnen GJC, Windhorst AD, Boellaard R, Oprea-Lager DE, Menke-van der Houven van Oordt CW. The Diagnostic Accuracy of 18F-FDG PET and 18F-FES PET for Staging Grade 1-2 Estrogen Receptor-Positive Breast Cancer. Radiology. 2025 Mar;314(3):e241850. doi: 10.1148/radiol.241850.

    PubMed 40035673

  • Iqbal R, Menke-van der Houven van Oordt CW, Oprea-Lager DE, Booij J. [18F]FES uptake in the pituitary gland and white matter of the brain. Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):3009-3010. doi: 10.1007/s00259-021-05281-8. Epub 2021 Mar 17. No abstract available.

    PubMed 33730173

Questions about this trial

What is this clinical trial studying?

A study testing 18F-Fluorestradiol PET/CT scan in people with Breast Cancer, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03726931, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2023.

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