Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

May 3, 2024 updated by: University Medical Center Groningen

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713GZ
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Patients with a history of histological proven ER-positive primary breast cancer and, whenever available, histological proven ER-positive recurrence. 2. Post-menopausal status (age ≥ 45 years with amenorrhea for > 12 months or prior bilateral ovariectomy 3. Documentation of a negative pregnancy test must be available for women less than 2 years after menopause 4. Progressive disease after 2 lines of hormonal therapy 5. No previous fulvestrant treatment 6. ER-antagonists should be discontinued for 5 weeks prior to FES-PET to prevent false negative FES-PET results. The use of aromatase inhibitors is allowed 7. ECOG performance status 0, 1 or 2 8. Life expectancy > 3 months 9. Creatinine clearance ≥ 30 ml/min 10. Age ≥ 18 years 11. Signed written informed consent 12. Able to comply with the protocol

Exclusion Criteria:

  • 1. Evidence of central nervous system metastases 2. Presence of life-threatening visceral metastases 3. > 3 lines of endocrine therapy for metastatic disease 4. > 2 lines of chemotherapy in metastatic disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single arm
Fluoroestradiol-PET is performed at baseline, after 1 month, and 3 months
Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol
A FES-PET/(CT) will be performed thrice during protocol execution. Patients will be injected with ~200MBq 18F-FES

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy
Time Frame: baseline; 1 month; 3 months

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
baseline; 1 month; 3 months
To evaluate the proportion of patients with an incomplete down-regulation/occupancy of ERs as determined by FES-PET
Time Frame: baseline, 1 month and 3 months

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
baseline, 1 month and 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The feasibility to quantify changes in FES-uptake in liver metastases
Time Frame: baseline, 1 month and 3 months
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
baseline, 1 month and 3 months
to correlate FES-PET results to patient and tumor response on fulvestrant therapy
Time Frame: baseline, 1 month, 3 months

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
baseline, 1 month, 3 months
Explorative analysis to correlate several factors (among which tumor burden, ER-expression, fulvestrant levels, estradiol levels, patient weight) to FES uptake will be performed.
Time Frame: baseline, 1 month and 3 months
Explorative analysis to correlate several factors at different timepoints (baseline, 1 month, 3 months) to FES uptake.
baseline, 1 month and 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

May 19, 2011

First Submitted That Met QC Criteria

June 20, 2011

First Posted (Estimated)

June 21, 2011

Study Record Updates

Last Update Posted (Actual)

May 6, 2024

Last Update Submitted That Met QC Criteria

May 3, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RUG2010-2611

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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