Clinical trial NCT04824014: 4FMFES-PET Imaging of ER+ Advanced Breast Cancers
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: ER+ Breast Cancer
Lead sponsor: Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Society (CCS)
name: Université de Sherbrooke
First posted: 2021-04-01
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility 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.

Primary outcomes:
measure: Correlation of 4FMFES-PET uptake with histopathological markers, notably ER immunohistochemistry (IHC) score
timeFrame: 18 months
measure: Evaluation of progression-free survival versus 4FMFES-PET uptake threshold
timeFrame: 18 months
measure: Evaluation of time-to-recurrence versus 4FMFES-PET uptake threshold
timeFrame: 18 months
measure: Correlation of treatment response with reduction of 4FMFES-PET uptake and number of assessable lesions at 6 and 18 months after the initial assessment
timeFrame: 18 months
measure: Complementarity analysis of FDG-PET with 4FMFES-PET
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Université deSherbrooke
state: Quebec
Study officials:
affiliation: Université de Sherbrooke, Centre de Recherche du CHUS
name: Eric E Turcotte, MD
role: PRINCIPAL_INVESTIGATOR
References: