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4FMFES-PET Imaging of ER+ Advanced Breast Cancers

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ClinicalTrials.gov Identifier: NCT04824014
Recruitment Status : Recruiting
First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Collaborators:
Canadian Cancer Society (CCS)
Université de Sherbrooke
Information provided by (Responsible Party):
Dr Éric E Turcotte, MD, Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Brief 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. 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:

  1. 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;
  2. Correlate 4FMFES/FDG uptake and staging with pathological data (histology, receptor status, grade), including distal biopsy metastases sampling;
  3. 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.

Condition or disease Intervention/treatment Phase
ER+ Breast Cancer Diagnostic Test: 4FMFES-PET Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Actual Study Start Date : November 1, 2020
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 4FMFES-PET imaging at 0, 6 and 18 months
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.
Diagnostic Test: 4FMFES-PET
Intravenous 4FMFES injection, followed with PET imaging
Other Name: 4,16α-[16α-18F]difluoro-11β-methoxyestradiol PET




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


  5. 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.




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

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.

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): NCT04824014


Contacts
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Contact: Michel Paquette, PhD 819-346-1110 ext 11-982 michel.paquette@usherbrooke.ca
Contact: Stéphanie Dubreuil 819-346-1110 ext 16617 Stephanie.Dubreuil2@usherbrooke.ca

Locations
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Canada, Quebec
Université deSherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1H5N4
Contact: Eric E Turcotte, MD    346-1110 ext 11887    eric.e.turcotte@usherbrooke.ca   
Contact: Michel Paquette, PhD    819-346-1110 ext 11982    michel.paquette@usherbrooke.ca   
Sub-Investigator: Brigitte Guérin, PhD         
Sub-Investigator: Michel Pavic, MD         
Sub-Investigator: Guy-Anne Turgeon, MD         
Sub-Investigator: Étienne Rousseau, MD         
Sponsors and Collaborators
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Canadian Cancer Society (CCS)
Université de Sherbrooke
Investigators
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Principal Investigator: Eric E Turcotte, MD Université de Sherbrooke, Centre de Recherche du CHUS
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Responsible Party: Dr Éric E Turcotte, MD, MD, FRCPC, Head of clinical research, CIMS, CRCHUS, Centre de recherche du Centre hospitalier universitaire de Sherbrooke
ClinicalTrials.gov Identifier: NCT04824014    
Other Study ID Numbers: CIMS-4FMFES-2021-3966
First Posted: April 1, 2021    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases