Study to Determine the Utility of FES-PET in the Prediction of Response to Fulvestrant in Women With Estrogen Positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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Effects of fulvestrant on the ERs may be evaluable by molecular imaging using positron emission tomography with the ER-specific FES tracer. In this study we will determine the utility of FES-PET in the prediction of response to fulvestrant 500 mg in women with estrogen positive metastatic breast cancer

Detailed Description
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More than 70% of patients with metastatic breast cancer present with hormone receptor positive disease and for whom hormonal therapy is the preferred treatment approach. First-line treatment recommendations for women with hormone receptor positive locally advanced or metastatic disease includes a generation aromatase inhibitors or tamoxifen. Fulvestrant, a 17β-estradiol analog, is an antiestrogen that suppresses estrogen signaling by binding to ER and inducing oestrogen receptor degradation and has estrogen antagonistic activity but no estrogen agonistic effect. Fulvestrant has been shown to have superiority over other endocrine therapy in a series of randomized controlled trials. The whole-body imaging of the availability of ER using FES-PET may prove valuable to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This potentially allows early prediction of therapy efficacy to fulvestrant in women with estrogen positive metastatic breast cancer. In this pilot-study we will evaluate 35 patients who received fulvestrant as treatment for metastatic breast cancer. All patients will undergo FES-PET/CT at baseline and FES-PET after 28 days. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.

Official Title
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Fluorine-18 Fluoroestradiol Positron Emission Tomography-computed Tomography: an in Vivo Biomarker Predicting Response to Fulvestrant in Women With Estrogen Positive Metastatic Breast Cancer?

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Fluoroestradiol (18F)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a history of histological proven ER-positive primary breast cancer and, whenever available, histological proven ER-positive recurrence. No previous fulvestrant treatment ER-antagonists should be discontinued for 5 weeks prior to FES-PET. The use of aromatase inhibitors is allowed. Age > 18 ECOG 0-2 Life expectancy > 6 months Informed consent obtained Able to comply with the protocol Exclusion Criteria: Presence of life-threatening visceral metastases Evidence of central nervous system metastases > 3 lines of endocrine therapy for metastatic disease Isolated liver metastasis (high FES uptake by normal liver)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients will undergo FES-PET/CT at baseline and FES-PET after 28 days of fulvestrant treatment. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fulvestrant<br>500mg fulvestrant on days 0, 14, 28 and every 28 days thereafter Fluoroestradiol-PET is performed at baseline and after 28 days | Drug: Fluoroestradiol (18F)<br>* A FES-PET/(CT) will be performed twice during protocol execution. Patients will be injected with approximately 222 MBq 18F-FES each time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the accuracy of the change of FES uptake in predicting progression-free survival(PFS) in patients treated with fulvestrant 500 mg | The FES-uptake will be calculated for all tumor lesions in individual patient at baseline and 28 days. Therapy response will be monitored by regular follow-up. RECIST criteria and clinical benefit will be used as criteria. All patients will be followed up until disease progression. | baseline; 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the heterogeneity of ER among different metastatic sites in breast cancer patients in vivo |  | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fulvestrant 500 mg, fluorine-18 fluoroestradiol PET-CT