FES PET/CT in Predicting Response in Patients With Newly Diagnosed Metastatic Breast Cancer Receiving Endocrine Therapy

NCT ID: NCT02398773

Last Updated: 2026-02-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-04

Study Completion Date

2026-03-31

Brief Summary

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This phase II trial studies F-18 16 alpha-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) in predicting response to endocrine therapy in patients with newly diagnosed breast cancer that has spread to other parts of the body. FES is a radioactive form of the hormone estrogen and may "light up" where cancer is in the body. Diagnostic procedures using FES, such as FES PET/CT, may help measure the FES and help doctors predict how well the cancer will respond to treatment.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the negative predictive value (NPV) of \[18F\]fluoroestradiol (FES) uptake for response (clinical benefit) at 6 months in patients with estrogen-receptor positive (ER+) metastatic breast cancer treated with first-line endocrine therapy.

SECONDARY OBJECTIVES:

I. To determine the test-retest reproducibility of quantitative assessment of tumor FES uptake by standardized uptake values (SUVs).

II. To evaluate the accuracy of FES-PET/CT for predicting response in patients treated with first line endocrine therapy for metastatic breast cancer.

III. To evaluate the accuracy of FES-PET/CT for predicting progression-free survival (PFS) in patients treated with first line endocrine therapy for metastatic breast cancer.

IV. To examine the role of FES-PET/CT in predicting progressive disease (PD) or clinical benefit (CB), in concert with semi-quantitative interpretation of ER, progesterone receptor (PgR), and marker of proliferation Ki-67 (Ki-67).

V. To evaluate the relationships among FES uptake, as measured by maximum SUV (SUVmax) and semi-quantitative ER from immunohistochemistry (IHC).

VI. To evaluate FES SUVmax \< 1.5 as the optimal cutpoint for predicting progression-free survival (PFS) to first line endocrine therapy for metastatic breast cancer.

VII. To determine the percent of eligible patients for whom biopsy is not feasible, i.e., determine the clinical utility of indirect assay of ER expression by FES-PET/CT.

VIII. To evaluate the heterogeneity of tumor FES uptake in individual patients defined as variability in lesion's FES uptake.

OUTLINE:

Between 0 to 30 days before start of endocrine therapy, patients receive F-18 16 alpha-fluoroestradiol intravenously (IV) over 2 minutes and undergo PET/CT. Patients may undergo a second FES-PET/CT study at least 24 hours after the first study and no later than 10 days after the initial study.

After completion of study, patients are followed up for 6 months and then periodically for up to 2 years.

Conditions

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HER2/Neu Negative Progesterone Receptor Negative Progesterone Receptor Positive Stage IV Breast Cancer AJCC v6 and v7

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Diagnostic (FES PET/CT)

Between 0 to 30 days before start of endocrine therapy, patients receive F-18 16 alpha-fluoroestradiol IV over 2 minutes and undergo PET/CT. Patients may undergo a second FES-PET/CT study at least 24 hours after the first study and no later than 10 days after the initial study.

Group Type EXPERIMENTAL

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT

F-18 16 Alpha-Fluoroestradiol

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Interventions

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Computed Tomography

Undergo PET/CT

Intervention Type PROCEDURE

F-18 16 Alpha-Fluoroestradiol

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Other Intervention Names

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CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography 16 alpha-fluroestradiol-17 beta F-18 FES FES Fluorine-18 16 alpha-fluoroestradiol Fluoroestradiol F-18 Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT

Eligibility Criteria

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Inclusion Criteria

* Capable and willing to provide informed consent
* Women must not be pregnant or breast-feeding. All females of childbearing potential must have a blood test or urine study within 7 days prior to FES PET/CT scan and \[18F\]-fluorodeoxyglucose (FDG)-PET/CT scan to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:

* Has not undergone a hysterectomy or bilateral oophorectomy or
* Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
* Patient is a postmenopausal woman, man, or premenopausal woman for whom standard endocrine therapy alone (tamoxifen, aromatase inhibitor \[AI\], with or without ovarian suppression or fulvestrant) is planned after FES-PET/CT is completed
* Medically stable as judged by patient's physician
* Life expectancy must be estimated by patient's physician at \> 6 months
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 (restricted to ECOG performance status \[PS\] 0-2 if age \> 70 years)
* Patient must NOT have a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FES
* Patient must NOT be in liver failure as judged by the patient's physician
* Histologically confirmed metastatic breast cancer
* Primary tumor and/or metastatic site must be ER+ and may be progesterone-receptor positive (PgR+) or progesterone-receptor negative (PgR-) by IHC; patients with a history of an estrogen-receptor negative (ER-) primary tumor and a documented ER+ metastatic site are eligible
* The pathology report and either (1) tissue (blocks or an unstained slides) or (2) a photomicrograph of the ER IHC slides from at least one site of metastatic disease and/or from primary breast cancer must be available for central review and analysis

* NOTE: if photomicrographs are submitted, the submission of hematoxylin and eosin (H\&E), PR and Ki67 IHC's, if performed, are also to be submitted
* Patient must NOT have human epidermal growth factor-2 positive (HER2+) metastatic disease
* Patient must NOT be planning to receive molecular targeted therapy (such as everolimus or palbociclib) nor HER2 directed therapy in addition to endocrine therapy
* Patient must NOT have received prior endocrine therapy for metastatic disease (i.e., must be first-line endocrine therapy for metastatic disease)
* Patient is not now, and never has received adjuvant endocrine therapy OR patient is currently receiving or has received adjuvant endocrine therapy in the past, AND adjuvant endocrine therapy was initiated \> 2 years prior to diagnosis of metastatic disease

* Note: patients who developed metastatic disease while still receiving adjuvant endocrine therapy must have a planned change in the type of endocrine agent used for subsequent metastatic disease treatment; patient is not receiving blocking adjuvant therapy (such as toremifene or tamoxifen) OR patient is receiving blocking adjuvant therapy, but will stop this therapy a minimum of 60 days prior to FES-PET/CT while still complying with the study timeline
* Patient must NOT have a history of \> 1 line of administered chemotherapy for metastatic disease and must be off chemotherapy for a minimum of 2 weeks; prior chemotherapy in the adjuvant setting is allowed
* Disease may be measurable (by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) or non-measurable but must be present in at least one non-liver site, where presence is defined as 1.5 cm or greater and visualized on PET/CT with \[18F\]-fluorodeoxyglucose (FDG); patients with effusion only disease or disease only in the liver are not eligible for the study
* Patient must be able to lie still for a 20-30 minute PET/CT scan
* Patient must NOT weigh more than the maximum weight limit for the table for the PET/CT scanner at the institution where the study is being performed
* The patient is participating in the trial at an institution which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined scanner qualification procedures and received ECOG-ACRIN (or current ACRIN) approval
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Farrokh Dehdashti

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Los Angeles General Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Sidney and Lois Eskenazi Hospital

Indianapolis, Indiana, United States

Site Status

Springmill Medical Center

Indianapolis, Indiana, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mount Sinai Hospital

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Fox Chase Cancer Center - East Norriton Hospital Outpatient Center

East Norriton, Pennsylvania, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, United States

Site Status

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, United States

Site Status

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin, United States

Site Status

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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EAI142

Identifier Type: -

Identifier Source: secondary_id

NCI-2015-00383

Identifier Type: REGISTRY

Identifier Source: secondary_id

PEAI142_R01PAPP01

Identifier Type: -

Identifier Source: secondary_id

EAI142

Identifier Type: OTHER

Identifier Source: secondary_id

EAI142

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2015-00383

Identifier Type: -

Identifier Source: org_study_id

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