ER+ Breast CancerPhase 2NCT04824014
4FMFES-PET Imaging of ER+ Advanced Breast Cancers
A Phase 2 study testing 4FMFES-PET in people with ER+ Breast Cancer, run by Centre de recherche du Centre hospitalier universitaire de Sherbrooke at 1 site in Canada.
Trial summary
Estrogen Receptor (ER) is a crucial prognostic factor and treatment target in breast cancer patients. Knowledge of its status greatly influences the choice of the optimal course of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ER+ Breast Cancer
- What is being tested?
- 4FMFES-PET
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2020to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced breast cancer patients, i.e. stage 3 or 4 diseases.
- Aged 18 or older at the time of breast cancer diagnosis.
- Histopathologic review confirming diagnosis of ER positive breast cancer.
- Male patients, although rare, can participate.
- Patient must have given informed consent.
- ECOG performance status 0-3.
Show all 9Show fewer
- ER must be positive in at least 10% of tumor cells in either the core biopsy or a therapeutic surgical resection.
- Any HER2-neu status.
- Patient eligible for and willing to receive systemic treatment.
Who cannot join
- Patients who are pregnant or nursing.
- Patients unable to tolerate PET/CT for 30 minutes.
- Patients taking anti-ER hormone therapy that can pharmacologically blockade estrogen receptors (ex: Tamoxifen, Fulvestrant). Patients can undergo 4FMFES-PET if anti-ER therapy was interrupted at least 8 weeks prior imaging. Aromatase inhibitors and LHRH analogs are not expected to interfere with 4FMFES uptake and are thus permitted to be taken prior and during this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Université deSherbrooke
Sherbrooke, Quebec, J1H5N4
Eric E Turcotte, MD, 346-1110 ext. 11887, eric.e.turcotte@usherbrooke.ca
Michel Paquette, PhD, 819-346-1110 ext. 11982, michel.paquette@usherbrooke.ca
About this study
Official title: Evaluation of the Diagnostic, Prognostic and Follow-up Potential of 4,16α-[16α-18F]Difluoro-11β-methoxyestradiol (4FMFES) PET Imaging for Estrogen Receptor Positive Advanced Breast Cancers
Estrogen Receptor (ER) is a crucial prognostic factor and treatment target in breast cancer patients. Knowledge of its status greatly influences the choice of the optimal course of treatment. Pathological evaluations of primary tumor, axillary nodes, and metastases are the only confirmatory approach to ER status determination and are limited to known and accessible sites. However, it is known that many advanced breast cancer patients harbor diseases presenting inter-tumor or temporal ER heterogeneity, as ER expression can vary between tumor foci and can evolve during treatment and at time of recurrence, hence the need for whole-body, non-invasive assessment of ER status.
In the last decades, 16α-[18F]fluoroestradiol (FES) was developed and evaluated as an ER-targeting positron emission tomography (PET) tracer. FES correlated with ER expression, and recently was shown to be able to predict hormone therapy response. Our Center designed and evaluated 4-fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES), a successor PET tracer for ER imaging. Paired comparison during a phase II clinical trial showed that 4FMFES produced images of better quality, with less overall non-specific signal than FES. It resulted in a significantly improved tumor contrast and tumor detectability using 4FMFES-PET leading to increased diagnosis confidence in early-stage breast cancer compared to FES-PET. Those results demonstrated that, as of now, 4FMFES-PET is the best imaging modality worldwide for whole-body ER status determination, but further validations are necessary to position this method as a standard and essential tool for breast cancer management. Like what was observed for FES-PET, preliminary data suggest that 4FMFES-PET combined with FDG-PET will yield very high sensibility for breast tumor detection, each method being complementary.
Read more
In continuity with previous work, we seek to expand our clinical knowledge of this high-potential diagnostic imaging through the following main objective:
Launch a phase II clinical trial to explore the full potential and benefit of 4FMFES-PET in combination with FDG-PET for advanced ER+ breast cancer patients to demonstrate it is an essential tool for cancer management.
This proposed project will focus on 3 specific aims:
- Compare and complement 4FMFES-PET with FDG-PET and conventional imaging modalities, and evaluate how they improved prognosis and staging of ER+ advanced breast cancer patients;
- Correlate 4FMFES/FDG uptake and staging with pathological data (histology, receptor status, grade), including distal biopsy metastases sampling;
- Correlate 4FMFES/FDG uptake and staging with longitudinal outcomes (treatment response, progression-free survival, time-to-relapse) to determine which cohort of patient benefit most from 4FMFES.
- Conditions
- ER+ Breast Cancer
- Being tested
- 4FMFES-PET
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4FMFES-PETDiagnostic test
Also called 4,16α-[16α-18F]difluoro-11β-methoxyestradiol PET
Intravenous 4FMFES injection, followed with PET imaging
| Study group | Role | What they receive |
|---|---|---|
| 4FMFES-PET imaging at 0, 6 and 18 months | Experimental | Patients burdened with ER+ advanced breast cancers and recruited in the trial will undergo an experimental 4FMFES-PET imaging within a 4-week interval of a medically-prescribed FDG-PET. The 4FMFES-PET procedure will be repeated at 6 and 18 months following the initial scan. Receives: Diagnostic Test: 4FMFES-PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of 4FMFES-PET uptake with histopathological markers, notably ER immunohistochemistry (IHC) score
4FMFES-PET targets Estrogen Receptors (ER) in ER+ cancers with high affinity, at least in vitro. 4FMFES-PET was already compared to the similar PET tracer FES, whose uptake is known to correlate with ER status and IHC score, and shown to have superior diagnostic properties. 4FMFES-PET will now be correlated with the ER IHC score, along with other histopathological markers.
Measured: 18 months
Evaluation of progression-free survival versus 4FMFES-PET uptake threshold
This outcome aims to evaluate the prognostic potential of 4FMFES-PET. Kaplan-Meyer curves of progression-free-survival (PFS) will be drawn, with the studied population separated with A) a 4FMFES-PET SUVMax cut-off value of 1.5; and B) FDG-PET/4FMFES-PET tumor ratio cutoff value of 2.0, each for the lowest uptake tumor within the same patient at the initial assessment. It is expected that higher 4FMFES uptake and lower FDG/4FMFES ratio will be associated with better outcome for patients.Significant differences will be evaluated using the Log-Rank test.
Measured: 18 months
Evaluation of time-to-recurrence versus 4FMFES-PET uptake threshold
This outcome aims to evaluate the prognostic potential of 4FMFES-PET. Kaplan-Meyer curves of time-to-recurrence (TTR) will be drawn, with the studied population separated with A) a 4FMFES-PET SUVMax cut-off value of 1.5; and B) FDG-PET/4FMFES-PET tumor ratio cutoff value of 2.0, each for the lowest uptake tumor within the same patient at the initial assessment. It is expected that higher 4FMFES uptake and lower FDG/4FMFES ratio will be associated with better outcome for patients.Significant differences will be evaluated using the Log-Rank test.
Measured: 18 months
Correlation of treatment response with reduction of 4FMFES-PET uptake and number of assessable lesions at 6 and 18 months after the initial assessment
All patients on the study will be followed longitudinally with clinical questionnaire and examination as of their treating oncologist. Clinical information on treatment details, first progression and site of progression will be recorded on a follow-up form at each visit for at least 3 years. All stage 3 breast cancer patients with a breast in place will undergo annual mammograms with or without breast ultrasound as of current standard practice.
Patients receiving chemo-, radio and/or hormone therapy will be longitudinally followed-up using 4FMFES-PET and FDG-PET at 6 months and 18 months following the initial scan. Imaging at shorter intervals could also be done if deemed necessary. Tracer uptake, number and size of lesions will be documented at each imaging.
If it occurs, case of death will be sought from hospital or community medical records.
Measured: 18 months
Complementarity analysis of FDG-PET with 4FMFES-PET
4FMFES-PET will be scheduled within two weeks of a clinically prescribed FDG-PET to allow 4FMFES to FDG comparison.
Uptake (SUV: Standardized Uptake Value) and contrast (tumor SUVMax / background SUVMean ratio) will be measured and compiled for each lesion. Detection of each lesion will be determined by the contrast value: 1) higher or equal to 3 = positive; 2) between 1.5 and 3 = ubiquitous; 3) under 1.5 = negative. A study will be considered as 4FMFES-negative if 4FMFES-PET does not display any focal uptake other than normal physiological biodistribution, and the same will be done for FDG-PET. Unsuspected lesion visible on 4FMFES-PET or FDG-PET will be investigated by biopsy when possible to prove the lesion's histopathology. Follow-up images will be compared with the initial FDG and 4FMFES-PET scans for each patient, and both the total number of visible tumors and their uptake will be compared between each time point.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2021
- Study start1 Nov 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ER+ Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre de recherche du Centre hospitalier universitaire de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Cancer Society (CCS), Université de Sherbrooke
- Responsible party
- Principal investigator, Dr Éric E Turcotte, MD, Centre de recherche du Centre hospitalier universitaire de Sherbrooke
- Investigators
- Eric E Turcotte, MD, Principal investigator, Université de Sherbrooke, Centre de Recherche du CHUS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04824014
- Sponsor's protocol ID
- CIMS-4FMFES-2021-3966
- Status last verified
- Jul 2026
- First submitted
- 24 Mar 2021
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Diagnostic, Prognostic and Follow-up Potential of 4,16α-[16α-18F]Difluoro-11β-methoxyestradiol (4FMFES) PET Imaging for Estrogen Receptor Positive Advanced Breast Cancers
- ClinicalTrials.gov ID
- NCT04824014
- Acronym / sponsor ID
- CIMS-4FMFES-2021-3966
- Conditions
- ER+ Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Centre de recherche du Centre hospitalier universitaire de SherbrookeUniversity, hospital or other
- Collaborators
- Canadian Cancer Society (CCS), Université de Sherbrooke
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 1 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Estrogen Receptor (ER) is a crucial prognostic factor and treatment target in breast cancer patients. Knowledge of its status greatly influences the choice of the optimal course of treatment. Pathological evaluations of primary tumor, axillary nodes, and metastases are the only confirmatory approach to ER status determination and are limited to known and accessible sites. However, it is known that many advanced breast cancer patients harbor diseases presenting inter-tumor or temporal ER heterogeneity, as ER expression can vary between tumor foci and can evolve during treatment and at time of recurrence, hence the need for whole-body, non-invasive assessment of ER status.
In the last decades, 16α-[18F]fluoroestradiol (FES) was developed and evaluated as an ER-targeting positron emission tomography (PET) tracer. FES correlated with ER expression, and recently was shown to be able to predict hormone therapy response. Our Center designed and evaluated 4-fluoro-11β-methoxy-16α-[18F]fluoroestradiol (4FMFES), a successor PET tracer for ER imaging. Paired comparison during a phase II clinical trial showed that 4FMFES produced images of better quality, with less overall non-specific signal than FES. It resulted in a significantly improved tumor contrast and tumor detectability using 4FMFES-PET leading to increased diagnosis confidence in early-stage breast cancer compared to FES-PET. Those results demonstrated that, as of now, 4FMFES-PET is the best imaging modality worldwide for whole-body ER status determination, but further validations are necessary to position this method as a standard and essential tool for breast cancer management. Like what was observed for FES-PET, preliminary data suggest that 4FMFES-PET combined with FDG-PET will yield very high sensibility for breast tumor detection, each method being complementary.
In continuity with previous work, we seek to expand our clinical knowledge of this high-potential diagnostic imaging through the following main objective:
Launch a phase II clinical trial to explore the full potential and benefit of 4FMFES-PET in combination with FDG-PET for advanced ER+ breast cancer patients to demonstrate it is an essential tool for cancer management.
This proposed project will focus on 3 specific aims:
- Compare and complement 4FMFES-PET with FDG-PET and conventional imaging modalities, and evaluate how they improved prognosis and staging of ER+ advanced breast cancer patients;
- Correlate 4FMFES/FDG uptake and staging with pathological data (histology, receptor status, grade), including distal biopsy metastases sampling;
- Correlate 4FMFES/FDG uptake and staging with longitudinal outcomes (treatment response, progression-free survival, time-to-relapse) to determine which cohort of patient benefit most from 4FMFES.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 4FMFES-PET imaging at 0, 6 and 18 months | Experimental | Diagnostic Test: 4FMFES-PETPatients burdened with ER+ advanced breast cancers and recruited in the trial will undergo an experimental 4FMFES-PET imaging within a 4-week interval of a medically-prescribed FDG-PET. The 4FMFES-PET procedure will be repeated at 6 and 18 months following the initial scan. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Advanced breast cancer patients, i.e. stage 3 or 4 diseases.
- Aged 18 or older at the time of breast cancer diagnosis.
- Histopathologic review confirming diagnosis of ER positive breast cancer.
- Male patients, although rare, can participate.
- Patient must have given informed consent.
Key exclusion criteria (3 listed)
- Patients who are pregnant or nursing.
- Patients unable to tolerate PET/CT for 30 minutes.
- Patients taking anti-ER hormone therapy that can pharmacologically blockade estrogen receptors (ex: Tamoxifen, Fulvestrant). Patients can undergo 4FMFES-PET if anti-ER therapy was interrupted at least 8 weeks prior imaging. Aromatase inhibitors and LHRH analogs are not expected to interfere with 4FMFES uptake and are thus permitted to be taken prior and during this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4FMFES-PETAlso: 4,16α-[16α-18F]difluoro-11β-methoxyestradiol PETIntravenous 4FMFES injection, followed with PET imaging | Diagnostic test | 4FMFES-PET imaging at 0, 6 and 18 months |
Primary outcome
Correlation of 4FMFES-PET uptake with histopathological markers, notably ER immunohistochemistry (IHC) score
Time frame: 18 months
4FMFES-PET targets Estrogen Receptors (ER) in ER+ cancers with high affinity, at least in vitro. 4FMFES-PET was already compared to the similar PET tracer FES, whose uptake is known to correlate with ER status and IHC score, and shown to have superior diagnostic properties. 4FMFES-PET will now be correlated with the ER IHC score, along with other histopathological markers.
Evaluation of progression-free survival versus 4FMFES-PET uptake threshold
Time frame: 18 months
This outcome aims to evaluate the prognostic potential of 4FMFES-PET. Kaplan-Meyer curves of progression-free-survival (PFS) will be drawn, with the studied population separated with A) a 4FMFES-PET SUVMax cut-off value of 1.5; and B) FDG-PET/4FMFES-PET tumor ratio cutoff value of 2.0, each for the lowest uptake tumor within the same patient at the initial assessment. It is expected that higher 4FMFES uptake and lower FDG/4FMFES ratio will be associated with better outcome for patients.Significant differences will be evaluated using the Log-Rank test.
Evaluation of time-to-recurrence versus 4FMFES-PET uptake threshold
Time frame: 18 months
This outcome aims to evaluate the prognostic potential of 4FMFES-PET. Kaplan-Meyer curves of time-to-recurrence (TTR) will be drawn, with the studied population separated with A) a 4FMFES-PET SUVMax cut-off value of 1.5; and B) FDG-PET/4FMFES-PET tumor ratio cutoff value of 2.0, each for the lowest uptake tumor within the same patient at the initial assessment. It is expected that higher 4FMFES uptake and lower FDG/4FMFES ratio will be associated with better outcome for patients.Significant differences will be evaluated using the Log-Rank test.
Correlation of treatment response with reduction of 4FMFES-PET uptake and number of assessable lesions at 6 and 18 months after the initial assessment
Time frame: 18 months
All patients on the study will be followed longitudinally with clinical questionnaire and examination as of their treating oncologist. Clinical information on treatment details, first progression and site of progression will be recorded on a follow-up form at each visit for at least 3 years. All stage 3 breast cancer patients with a breast in place will undergo annual mammograms with or without breast ultrasound as of current standard practice. Patients receiving chemo-, radio and/or hormone therapy will be longitudinally followed-up using 4FMFES-PET and FDG-PET at 6 months and 18 months following the initial scan. Imaging at shorter intervals could also be done if deemed necessary. Tracer uptake, number and size of lesions will be documented at each imaging. If it occurs, case of death will be sought from hospital or community medical records.
Complementarity analysis of FDG-PET with 4FMFES-PET
Time frame: 36 months
4FMFES-PET will be scheduled within two weeks of a clinically prescribed FDG-PET to allow 4FMFES to FDG comparison. Uptake (SUV: Standardized Uptake Value) and contrast (tumor SUVMax / background SUVMean ratio) will be measured and compiled for each lesion. Detection of each lesion will be determined by the contrast value: 1) higher or equal to 3 = positive; 2) between 1.5 and 3 = ubiquitous; 3) under 1.5 = negative. A study will be considered as 4FMFES-negative if 4FMFES-PET does not display any focal uptake other than normal physiological biodistribution, and the same will be done for FDG-PET. Unsuspected lesion visible on 4FMFES-PET or FDG-PET will be investigated by biopsy when possible to prove the lesion's histopathology. Follow-up images will be compared with the initial FDG and 4FMFES-PET scans for each patient, and both the total number of visible tumors and their uptake will be compared between each time point.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for ER+ Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer
Active, not recruitingObservational study
Longitudinal ctDNA Surveillance for Older Women With ER+ Breast Cancer Who Omit Surgery
Breast Cancer
Recruiting
Signatera-Guided CDK4/6 Inhibitor Therapy in Breast Cancer
Breast Neoplasms, Carcinoma, Ductal, Breast
RecruitingPhase 2
A Phase 2 Bridging Study of Elacestrant Monotherapy in Advanced or Metastatic Breast Cancer
Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eric E Turcotte, MD principal investigator
Université de Sherbrooke, Centre de Recherche du CHUS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 4FMFES-PET in people with ER+ Breast Cancer, run by Centre de recherche du Centre hospitalier universitaire de Sherbrooke at 1 site in Canada.
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 9 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 10 Jul 2026. 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 Canada. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michel Paquette, PhD (819-346-1110 ext. 11-982, michel.paquette@usherbrooke.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of 4FMFES-PET uptake with histopathological markers, notably ER immunohistochemistry (IHC) score (time frame: 18 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jul 2026.