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HER2/Neu NegativePhase 2NCT02398773

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

A Phase 2 study testing Computed Tomography, F-18 16 Alpha-Fluoroestradiol and Laboratory Biomarker Analysis in people with HER2/Neu Negative and Progesterone Receptor Negative, run by National Cancer Institute (NCI) at 25 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Computed Tomography, F-18 16 Alpha-Fluoroestradiol and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
99 participants
Where
25 sitesUnited States
Study dates
4 May 2016to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 25Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Fox Chase Cancer Center - East Norriton Hospital Outpatient Center

    East Norriton, Pennsylvania, 19401

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Sidney and Lois Eskenazi Hospital

    Indianapolis, Indiana, 46202

  • Springmill Medical Center

    Indianapolis, Indiana, 46290

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Mount Sinai Hospital

    New York, New York, 10029

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • ProHealth Waukesha Memorial Hospital

    Waukesha, Wisconsin, 53188

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

Other trials in United States

About this study

Official title: [18F] Fluoroestradiol (FES) PET as a Predictive Measure for Endocrine Therapy in Patients With Newly Diagnosed Metastatic Breast Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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).

  1. 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.

Being tested
Computed Tomography, F-18 16 Alpha-Fluoroestradiol, Laboratory Biomarker Analysis, Positron Emission Tomography

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET/CT

  • F-18 16 Alpha-FluoroestradiolDrug

    Also called 16 alpha-fluroestradiol-17 beta, F-18 FES, FES, Fluorine-18 16 alpha-fluoroestradiol

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT02398773
Study groupRoleWhat they receive
Diagnostic (FES PET/CT)ExperimentalBetween 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.
Receives: Procedure: Computed Tomography; Drug: F-18 16 Alpha-Fluoroestradiol; Other: Laboratory Biomarker Analysis; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Negative predictive value of 18F FES uptake for response (CB), defined as the proportion of patients with a negative FES test result who have progressive disease

    FES-PET results will be assessed as positive or negative by quantitative or qualitative criteria. FES SUVmax < 1.5 will be defined as quantitatively negative test result while one or more sites of active disease will be qualitatively negative test result. The reference standard is patient's tumor response categorized by either CB or PD at 6 months. As part of the preliminary analysis, rates of FES uptake negative results overall and next by tumor response status will be calculated. FES-PET test positive results will be compared in the two tumor response groups using a chi-square test.

    Measured: At 6 months

Secondary outcomes (8)

  1. Test-retest reproducibility of quantitative assessment of tumor FES uptake by SUVs

    The reproducibility of the two measurements of SUVs will be assessed by intra-class correlation coefficient and its 95% confidence interval (CI). Additionally, the coefficient of repeatability (CR) and the Bland-Altman plot will be used.

    Measured: Up to 6 months

  2. FES SUVmax

    The receiver operating characteristic (ROC) curve of FES SUVmax and its associated area under an ROC curve (AUC) will be estimated to predict tumor response (clinical benefit). Next, sensitivity and specificity of the dichotomized FES SUVmax (using a cutoff of 1.5) will be estimated non-parametrically, where sensitivity is the proportion of responders having FES SUVmax < 1.5 and specificity is the proportion of non-responders having FES SUVmax > 1.5.

    Measured: Up to 6 months

  3. Predictive accuracy of FES PET/CT for PFS, defined as the time from entry onto study until tumor progression or death from any cause

    To evaluate the predictive accuracy of FES PET, the time-dependent ROC curve of FES SUVmax at pre-specified time points (e.g. 6 months, 1 year) and its corresponding AUC will be estimated. Next, sensitivity and specificity of the dichotomized FES SUVmax (using a cutoff of 1.5) will be estimated in which reference standard is PFS status at pre-specified time points including 6 months and 1 year.

    Measured: Up to 1 year

  4. Significance of FES PET measures in predicting PD or CB, in concert with semi-quantitative interpretation of ER, PgR, and Ki-67

    Logistic regression analysis will be used to examine the effects of various FES PET measurements on clinical benefit. Predictors are semi-quantitative ER measure, PgR, and Ki-67 based on IHC. Significance of each FES PET measure will be determined by the odds ratio and its 95% CI.

    Measured: Baseline

  5. FES uptake, as measured by SUVmax and semi-quantitative ER from IHC

    The semi-quantitative ER measure will be obtained by using Allred score. The relationship between SUVmax and semi-quantitative ER measure will be evaluated by using a linear regression model treating SUVmax as a dependent variable and semi-quantitative ER measure as a predictor.

    Measured: Up to 6 months

  6. FES SUVmax < 1.5 as the optimal cutpoint for predicting PFS

    Time dependent ROC analysis will be performed to determine the optimal cutoff point for the FES SUVmax and to examine whether there is a more optimal cut-off for dichotomous interpretation of FES SUVmax than the current value 1.5. Specifically, the optimal cut-off point will be determined by maximizing Youden's index for the time dependent ROC curve at a pre-specified time point (e.g. 6 months, 1 year).

    Measured: Up to 1 year

  7. Percent of eligible patients for whom biopsy is not feasible, i.e., clinical utility of indirect assay of ER expression by FES PET

    The proportion of eligible patients for whom biopsy of a metastatic site is not feasible out of a total of 99 patients will be calculated.

    Measured: Up to 6 months

  8. Heterogeneity of tumor FES uptake in individual patients defined as variability in lesion's FES uptake

    Sample correlation matrix for the multiple SUV measurements will be calculated. Next, linear mixed effects model will be used where the outcome is SUV measurements and covariates include fixed effects (sites that the SUV value is measured and patient characteristics). Lesion-specific random effects will be added to the model. The correlations among SUV measurements will be calculated based on the fitted model.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2015 (estimated)
  2. Study start4 May 2016
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
99 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02398773
Sponsor's protocol ID
NCI-2015-00383
Other IDs
NCI-2015-00383, EAI142, PEAI142_R01PAPP01, EAI142, EAI142, U10CA180820
Status last verified
Jun 2026
First submitted
25 Mar 2015
Last updated
29 Jun 2026
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Computed Tomography, F-18 16 Alpha-Fluoroestradiol and Laboratory Biomarker Analysis in people with HER2/Neu Negative and Progesterone Receptor Negative, run by National Cancer Institute (NCI) at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Negative predictive value of 18F FES uptake for response (CB), defined as the proportion of patients with a negative FES test result who have progressive disease (time frame: At 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02398773.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.

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