Serial FES PET/CT to Measure Hormone Expression in Patients Undergoing Endocrine Targeted Therapy

OUTLINE:

Patients undergo F-18 FES PET/CT scan at baseline. Patients also undergo F-18 FES PET/CT and FDG PET/CT between 1-12 weeks after starting therapy, and then 1-12 weeks after the second FES PET/CT scan. Repeat FDG PET may be omitted in patients on selective estrogen receptor degrader.

After completion of study, patients are followed up for up to 20 years.

• F-18 16 Alpha-Fluoroestradiol (Drug), also known as F-18 FES, FES, Fluorine-18 16 alpha-fluoroestradiol, Fluoroestradiol F-18: Undergo F-18 FES PET/CT
• Positron Emission Tomography (Procedure), also known as Medical Imaging, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography: Undergo F-18 FES PET/CT
• Computed Tomography (Procedure), also known as CAT Scan, Computerized Axial Tomography, CT scan: Undergo F-18 FES PET/CT
• Fludeoxyglucose F-18 (Drug), also known as FDG, Fluorodeoxyglucose F18, 18FDG: Undergo FDG PET/CT
• Positron Emission Tomography (Procedure), also known as Medical Imaging, PET, PET Scan: Undergo FDG PET/CT
• Computed Tomography (Procedure), also known as CAT Scan: Undergo FDG PET/CT
• Laboratory Biomarker Analysis (Other): Correlative studies

Primary outcomes

• Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) - Avg SULmax [From time of first F-18 FES-PET/CT scan to time of second F-18 FES-PET/CT scan (approximately 1-12 weeks)]: FES uptake will be quantified using lean body mass adjusted SUV (SUL). Percentage change in FES average SULmax between baseline and a second FES scan will be calculated for up to 3 lesions per patient.
• F-18 16 Alpha-fluoroestradiol (FES) Uptake [From time of first F-18 FES-PET/CT scan to time of second F-18 FES-PET/CT scan (approximately 1-12 weeks)]: Quantitative measures of FES uptake for each disease site will be determined by drawing regions-of-interest on lesions to determine maximal FES uptake (SUVmax) per lesion. Up to 10 sites seen on the static torso survey will be quantified.
• Proportion of Patients With a Threshold of Percentage Change, or That Surpass a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) [From time of first F-18 FES-PET/CT scan to time of second F-18 FES-PET/CT scan (approximately 1-12 weeks)]: The number of patients showing a 20% increase in FES uptake (SULmean or SUVmax) compared to baseline from the first to second scan using a 90% Wilson score binomial confidence interval.

Secondary outcomes

• Time to Disease Progression [From start of therapy up to 20 years]: Time to disease progression will be measured as the time from the start of endocrine therapy to the time the patient is first recorded as having disease progression.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adult, non-pregnant patients with biopsy-proven or clinically obvious primary, recurrent or metastatic breast cancer
* Breast cancer from ER+ primary that is seen on other imaging tests. Tumor ER expression must have been confirmed by immunohistocytochemistry of primary tumor or recurrent disease.
* At least one site of disease 1.5 cm or greater is needed to meet the spatial resolution limits of PET imaging.
* Patients must have been off tamoxifen or other estrogen receptor blocking agents for at least 6 weeks and off chemotherapy for 3 weeks for the initial baseline FES.
* Patients must be selected for an endocrine targeted therapy regimen for treatment of their breast cancer by the referring oncologist. Selected treatments may be part of experimental treatment protocols for which the patient would be separately consented.
* Patients must be willing to undergo serial imaging procedures.
* Patients must agree to allow access to clinical records regarding response to treatment and long term follow up.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* An inability to lie still for the tests
* Individuals weighing more than 300 lb. (this is the weight limit of the scanner table)
* Pregnant or lactating. Women of childbearing potential with either a positive or no pregnancy test at baseline are excluded.
* Any other life-threatening illness (e.g. serious, uncontrolled concurrent infection or clinically significant cardiac disease - congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmia not well controlled with medication).
* Use of tamoxifen, faslodex, DES or any other ER blocking agent < 6 weeks or chemotherapy < 3 weeks prior to imaging scan.
* Uncontrolled diabetes mellitus (fasting glucose > 200 mg/dL)
* Adult patients who require monitored anesthesia for PET scanning.

Participant flow

Outcome results

• Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) - Avg SULmax (Primary), Mean, Percentage decrease in avgSUL: Diagnostic (F-18 FES PET/CT) 78 (77 to 79)
• F-18 16 Alpha-fluoroestradiol (FES) Uptake (Primary), Mean, average SUVmax: Diagnostic (F-18 FES PET/CT) 5.7 (4.6 to 6.8)
• Proportion of Patients With a Threshold of Percentage Change, or That Surpass a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV) (Primary), Number, participants with increased FES uptake: Diagnostic (F-18 FES PET/CT) 0
• Time to Disease Progression (Secondary)

Adverse events

Time frame: 24 hours after each FES PET/CT study (the time-frame of F18-FES decay)

• Study Protocol and Statistical Analysis Plan (PDF, 2020-09-25)
• Informed Consent Form (PDF, 2020-10-29)

• Hannah Linden, Principal investigator, Fred Hutch/University of Washington Cancer Consortium