Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Fulvestrant

Estrogens

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Hormones

Hormone Antagonists

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

Fluoroestradiol-PET is performed at baseline, after 1 month, and 3 months

A FES-PET/(CT) will be performed thrice during protocol execution. Patients will be injected with \~200MBq 18F-FES

Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol

The dose of fulvestrant to optimally downregulate estrogen receptors (ER) is currently subject of debate. Effects of fulvestrant on the ERs may be evaluable by molecular imaging using positron emission tomography with the ER-specific FES tracer. In this pilot study we will evaluate the effects of the new dose of fulvestrant (500mg i.m.)on the availability of ER binding sites in 15 metastatic breast cancer patients.

The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In these patients signaling via the ER induces proliferation and cell survival of malignant cells. Fulvestrant can inhibit this signaling route by blocking the receptor and decreasing ER-expression by increasing its turn-over rate.

The historical standard dose of fulvestrant was 250mg every 28 days i.m.; however studies performing serial biopsies showed that ER-downregulation was suboptimal. Recently the standard dose has been set to 500mg i.m. on day 1; 14; 28 and every 28 days thereafter. Although slightly more effective than the 250mg dose, still questions remain with respect to the required dose to establish maximal downregulation of ER-signaling.

Immunohistochemistry only provides static information, i.e. the level of ER-expression. However, dynamic information evaluating the effects of fulvestrant on occupancy of ERs, may also be valuable.

Whole-body imaging of the availability of ER binding sites using FES-PET may prove valuable to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This potentially allows adjustment of dosing in individual patients to aid therapy efficacy.

In this pilot-study we will evaluate 15 metastatic breast cancer patients. All patients will undergo FES-PET/CT at baseline, FES-PET after 1 month, and FES-PET/CT after three months. Hormone- and fulvestrant levels will be measured in all patients. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.

Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET

FES-uptake will be calculated for all tumor lesions at baseline, 1 month and 3 months.

Changes between FES-uptake during fulvestrant therapy will be calculated for:

* 3 months minus baseline
* 3 months minus 1 month
* 1 month minus baseline

FES-uptake will be calculated for all tumor lesions at baseline, after 1 month and after 3 months.

Incomplete down-regulation/ occupancy of ERs is defined as 1) an absolute SUV\> 1.5, and 2) a relative decrease in SUV of \<75% during fulvestrant therapy.

The proportion of patients that match these criteria will be given for:

* 1 month minus baseline
* 3 months minus baseline

Liver metastases detected on PET/CT will be serially quantified at the 3 different time points to evaluate the feasibility to quantify liver lesions on FES-PET/CT

Patients will be categorized as responders and non-responders by standard follow-up (monthly visits, 3-monthly CT, other techniques when indicated).

The predictive value of FES-PET for response to fulvestrant will be calculated for:

* baseline FES-uptake
* changes in FES-uptake from baseline to 1 month
* changes in FES-uptake from baseline to 3 months

Lesion-based evaluation will be performed for measurable lesions as defined by RECIST criteria, and changes in diameter will be correlated to changes in FES-uptake at:

* 1 month minus baseline
* 3 months minus baseline

Explorative analysis to correlate several factors at different timepoints (baseline, 1 month, 3 months) to FES uptake.

University Medical Center Groningen

All patients included in part A will receive a dynamic FES PET/CT scan.

All patients included in part B will receive a whole body static FES PET/CT scan twice within 1 week.

Catherina W Menke-van der Houven van Oordt, MD PhD

Data-management Medical Oncology

Ramsha Iqbal, MD

16a-18F-fluoro-17b-estradiol (\[18F\]FES) is radioactive labeled estradiol, developed for in vivo visualization of the estrogen receptor (ER) using positron emission tomography (PET). To date, \[18F\]FES PET has been mainly explored as a diagnostic imaging tool to assess ER expression, thereby identifying locations of disease and their potential sensitivity to endocrine therapy, respectively. The primary aim of this project is to extend the application of \[18F\]FES PET as a baseline diagnostic imaging biomarker for ER expression to use it as an (early) treatment response marker. However, for such an application, visual assessment alone may not be sufficient and a more rigorous quantitative image analysis is needed. Therefore, in this project we shall first derive the optimal pharmacokinetic model for full quantitative analysis of \[18F\]FES uptake and, subsequently, we shall assess the validity of simplified, clinically feasible, quantitative parameters of \[18F\]FES uptake in 5 patients with metastatic estrogen receptor positive (ER+) breast cancer (part A). In addition, the repeatability of these simplified parameters will then be investigated in another 10 patients (part B).

Dynamic and Test-retest Whole Body [18F]FES PET Imaging in Patients With Metastatic ER+ Breast Cancer

Repeatability of standardized uptake values and tumor-to-blood ratios will be assessed.

FES uptake in lesions will be expressed as Ki or VT values

Quantification of FES uptake in lesions will be assessed by determining standardized uptake values and tumor-to-blood ratios.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites	NCT01377324	Metastatic Brea...	Diagnostic inte...	18 Years -	University Medical Center Groningen
Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites	NCT01377324	Metastatic Brea...	Diagnostic inte...	18 Years -	University Medical Center Groningen
Dynamic and Test-retest Whole Body [18F]FES PET Imaging in Patients With Metastatic ER+ Breast Cancer	NCT05088785	Breast Cancer	FES	18 Years -	Amsterdam UMC, location VUmc

Spots Global Cancer Trial Database for fes

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Spots Global Cancer Trial Database for fes

Every month we try and update this database with for fes cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for fes cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.