F-18 FES PET/CT in Measuring Hormone Expression in Patients With Primary, Recurrent, or Metastatic Breast Cancer Undergoing Endocrine-Targeted Therapy

• Sponsor: University of Washington (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02149173
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 29
• Location: 1
• Arm: 1
• Actual Duration (Months): 124
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This clinical trial studies use of F-18 16 alpha-fluoroestradiol ([F-18] FES) positron emission tomography (PET)/computed tomography (CT) in measuring tumor hormone receptor expression in patients undergoing endocrine-targeted therapy for newly diagnosed breast cancer or breast cancer that has come back or spread to other places in the body. Comparing results of diagnostic procedures done before, during, and after hormone therapy may help measure a patient's response to treatment.

Condition or Disease	Intervention/Treatment	Phase
Estrogen Receptor Positive; Recurrent Breast Carcinoma; Stage IV Breast Cancer AJCC v6 and v7	Procedure: Computed Tomography; Procedure: Computed Tomography; Drug: F-18 16 Alpha-Fluoroestradiol; Drug: Fludeoxyglucose F-18; Other: Laboratory Biomarker Analysis; Procedure: Positron Emission Tomography; Procedure: Positron Emission Tomography	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. Measure the effect of endocrine targeted therapy on estrogen receptor (ER) expression and estradiol binding to the receptor using serial FES PET and fludeoxyglucose F-18 (FDG) PET.

SECONDARY OBJECTIVES:

1. Document the safety profile of FES PET in patients with breast cancer.

2. Examine associations between FES PET results and serial measurements of hormone or other levels in peripheral blood, as related to efficacy of endocrine-targeted therapy. Correlate FES PET uptake measures with histopathological assays and tumor microenvironment studies on biopsy specimens, if relevant to specific treatment regimen.

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Serial [F-18] Fluoroestradiol (FES) PET Imaging to Evaluate Endocrine-Targeted Therapy
• Actual Study Start Date: Sep 15, 2010
• Actual Primary Completion Date: Dec 27, 2018
• Actual Study Completion Date: Jan 13, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Diagnostic (F-18 FES PET/CT) 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.

Procedure: Computed Tomography; Undergo F-18 FES PET/CT; Other Names: CAT CAT Scan Computerized Axial Tomography computerized tomography CT CT SCAN tomography ; Procedure: Computed Tomography; Undergo FDG PET/CT; Other Names: CAT CAT Scan Computerized Axial Tomography computerized tomography CT CT SCAN tomography ; Drug: F-18 16 Alpha-Fluoroestradiol; Undergo F-18 FES PET/CT; Other Names: 16 alpha-fluroestradiol-17 beta F-18 FES FES Fluorine-18 16 alpha-fluoroestradiol Fluoroestradiol F-18 ; Drug: Fludeoxyglucose F-18; Undergo FDG PET/CT; Other Names: 18FDG FDG fludeoxyglucose F 18 Fludeoxyglucose F18 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose Fluorodeoxyglucose F18 ; Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Positron Emission Tomography; Undergo F-18 FES PET/CT; Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging ; Procedure: Positron Emission Tomography; Undergo FDG PET/CT; Other Names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging

Outcome Measures

Primary Outcome Measures

1. Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV [from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)]

   Uptake was quantified using lean body mass adjusted SUV (SULmean). The geometric mean was calculated for up to 3 lesions per patient. Systematic change in FES SULgmean between baseline and a second FES scan at approximately 2 or 8 weeks and a third FES scan was at approximately 8 weeks measured using a sign test where the median change is zero.

2. F-18 16 Alpha-fluoroestradiol (FES) Uptake [from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)]

   Quantitative and qualitative measures of FES uptake for each disease site, a set of 1.5 cm diameter regions on three adjacent planes with the highest lesion FES uptake will be drawn to determine maximal FES uptake. Up to 10 sites seen on the static torso survey will be quantified. Lesions will qualitatively determined to be visible or not visible.

3. Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed 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 or third F-18 FES-PET/CT scan (approximately 2-8 weeks)]

   The number of patients showing a 20% increase in FES SULgmean compared to baseline at either 2 or 8 weeks using a 90% Wilson score binomial confidence interval.

Secondary Outcome Measures

1. Time to Disease Progression [from start of therapy up to 20 years]

   Months from the start of endocrine therapy to the time the patient is first recorded as having disease progression,

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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, diethylstilbestrol (DES) or any other ER blocking agent < 6 weeks or chemotherapy < 3 weeks prior to imaging scan

• Unwillingness or inability to give informed consent

• Uncontrolled diabetes mellitus (fasting glucose > 200 mg/dL)

• Adult patients who require monitored anesthesia for PET scanning

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 20, 2019

More Information

Publications

None provided.

• Responsible Party: University of Washington
• ClinicalTrials.gov Identifier: NCT02149173
• Other Study ID Numbers: 7184; NCI-2013-02342; 7184; P01CA042045; U01CA148131; RG1711032
• First Posted: May 29, 2014
• Last Update Posted: Jun 30, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Deoxyglucose; Fluorodeoxyglucose F18; Fluorides

Study Results

Participant Flow

Arm/Group Title	Diagnostic (F-18 FES PET/CT)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	29
COMPLETED	29
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Diagnostic (F-18 FES PET/CT)
Arm/Group Description	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.
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 58.6%
>=65 years	12 41.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	29 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	29 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 10.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.4%
White	25 86.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Change in F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV), Assessed by a One-sample Test of the Percent Change in FES SUV
Description	Uptake was quantified using lean body mass adjusted SUV (SULmean). The geometric mean was calculated for up to 3 lesions per patient. Systematic change in FES SULgmean between baseline and a second FES scan at approximately 2 or 8 weeks and a third FES scan was at approximately 8 weeks measured using a sign test where the median change is zero.
Time Frame	from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)

Outcome Measure Data

Analysis Population Description

15/23 patients underwent a second FES PET/CT scan approximately 2 wks after starting potential ER modulating (vorinostat) therapy. 14/23 underwent a second or third FES PET/CT scan approximately 8 wks after starting vorinostat therapy. 6 patients underwent a second FES PET/CT scan between 2-8 wks after starting potential ER blocking therapy.

Arm/Group Title	FES-imaging After 2 Wks of ER Modulating (Vorinostat) Therapy	FES-imaging After 8 Wks of ER Modulating (Vorinostat) Therapy	FES-imaging After 2-8 Weeks of ER Blocking Therapy
Arm/Group Description	Patients undergo F-18 FES PET/CT and FDG PET/CT scans at baseline. Patients also undergo F-18 FES PET/CT between approximately 2 weeks after starting therapy	Patients undergo F-18 FES PET/CT and FDG PET/CT scans at baseline. Patients also undergo F-18 FES PET/CT between approximately 8 weeks after starting therapy	Patients undergo F-18 FES PET/CT and FDG PET/CT scans at baseline. Patients also undergo F-18 FES PET/CT between approximately 2-8 weeks after starting estrogen receptor blocking therapy.
Measure Participants	15	14	6
Median (Full Range) [percentage of change in SULgmean]	8.7	1.9	-60.3

2. Primary Outcome

Title	F-18 16 Alpha-fluoroestradiol (FES) Uptake
Description	Quantitative and qualitative measures of FES uptake for each disease site, a set of 1.5 cm diameter regions on three adjacent planes with the highest lesion FES uptake will be drawn to determine maximal FES uptake. Up to 10 sites seen on the static torso survey will be quantified. Lesions will qualitatively determined to be visible or not visible.
Time Frame	from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)

Outcome Measure Data

Analysis Population Description

quantitative and qualitative measure of FES positive lesions

Arm/Group Title	Quantitative Uptake	Qualitative Uptake
Arm/Group Description	number of lesions with quantitative uptake (SULmax) above 0.85 (the value indicating a negative lesion)	Number of lesions visually indicated as having FES uptake
Measure Participants	29	29
Measure number of ER+ lesions	314	314
Count of Units [number of ER+ lesions]	281	243

3. Primary Outcome

Title	Proportion of Patients Experienced a Threshold in Percentage Change, or Surpassed a Targeted Follow-up F-18 16 Alpha-fluoroestradiol (FES) Standardized Uptake Value (SUV)
Description	The number of patients showing a 20% increase in FES SULgmean compared to baseline at either 2 or 8 weeks using a 90% Wilson score binomial confidence interval.
Time Frame	from time of first F-18 FES-PET/CT scan to time of second or third F-18 FES-PET/CT scan (approximately 2-8 weeks)

Outcome Measure Data

Analysis Population Description

The patient arms different from Primary Outcome 1 because they are separated according to the type of therapy each group had (ER modulating or ER blocking), not by the number of FES scans that they had. Results are based on the change between 2 scans.

Arm/Group Title	FES With Potential ER Modulating Therapy (Vorinostat)	FES With Potential ER Blocking Therapy
Arm/Group Description	Patients undergo F-18 FES PET/CT and FDG PET/CT scans at baseline. Patients also undergo F-18 FES PET/CT between 1-12 weeks after starting possible ER modulating therapy (vorinostat) and then 1-12 weeks after the second FES PET/CT scan.	Patients undergo F-18 FES PET/CT scan and FDG PET/CT at baseline. Patients also undergo F-18 FES PET/CT between 1-12 weeks after starting possible ER blocking therapy.
Measure Participants	23	6
Number (90% Confidence Interval) [Proportion of participants]	0 0%	0 NaN

4. Secondary Outcome

Title	Time to Disease Progression
Description	Months from the start of endocrine therapy to the time the patient is first recorded as having disease progression,
Time Frame	from start of therapy up to 20 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FES With Potential ER Modulating Therapy (Vorinostat)	FES With Potential ER Blocking Therapy
Arm/Group Description	Patients undergo F-18 FES PET/CT and FDG PET/CT scans at baseline. Patients also undergo F-18 FES PET/CT between 1-12 weeks after starting possible ER modulating therapy (vorinostat) and then 1-12 weeks after the second FES PET/CT scan.	Patients undergo F-18 FES PET/CT scan and FDG PET/CT at baseline. Patients also undergo F-18 FES PET/CT between 1-12 weeks after starting possible ER blocking therapy.
Measure Participants	23	6
Median (Full Range) [months]	2	5.6

Adverse Events

Time Frame	Patients were monitored after each injection of FES for 24 hours (up to 3 injections over approximately 8 weeks)
Adverse Event Reporting Description	This is an imaging study. No adverse events are expected or have been reported due to tracer injection or imaging. All deaths were due to the natural course of metastatic breast cancer after the time period that adverse events were collected for this study. Any adverse events due to therapy are reported in a separate study in which these patients were co-enrolled (ID: 7841) and Sanofi TED14856 (SAR439859)
Arm/Group Title	Diagnostic (F-18 FES PET/CT)
Arm/Group Description	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.
All Cause Mortality
	Diagnostic (F-18 FES PET/CT)
	Affected / at Risk (%)	# Events
Total	24/29 (82.8%)
Serious Adverse Events
	Diagnostic (F-18 FES PET/CT)
	Affected / at Risk (%)	# Events
Total	0/29 (0%)
Other (Not Including Serious) Adverse Events
	Diagnostic (F-18 FES PET/CT)
	Affected / at Risk (%)	# Events
Total	0/29 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.