[18F]FES PET/CT Imaging for Uterine Cancer

Overseen By Shannon Long

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Tamoxifen, Fulvestrant

Disqualifiers: Pregnancy, Imaging intolerance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special imaging technique, called [18F]fluoroestradiol (FES) PET/CT, can assess estrogen receptor activity in women with recurrent or metastatic uterine cancer. The imaging occurs before starting a new treatment and may be repeated if the disease progresses to evaluate the cancer's response. Although the results might be shared with the doctor, they will not alter the treatment plan. Women with uterine cancer that has returned or spread, visible on standard scans, and who are managing this condition with their healthcare provider at the University of Pennsylvania, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are currently taking tamoxifen or fulvestrant, you will need to stop and wait for 8 weeks or 28 weeks, respectively, before the scan. For other medications, the protocol does not specify any requirements.

What prior data suggests that this imaging technique is safe for evaluating uterine cancer?

Research shows that [18F]fluoroestradiol (FES) PET/CT scans are generally easy for patients to handle. This imaging method has been used to check estrogen receptor activity in various cancers. Studies report that patients usually tolerate it well, and no serious side effects have been noted.

Most side effects are mild, such as slight dizziness or a minor headache, and they resolve on their own. Since [18F]FES is already used for other medical purposes, researchers have a good understanding of its safety. However, this trial will provide more specific safety information for its use in uterine cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of [18F]Fluoroestradiol (FES) PET/CT imaging for uterine cancer because it offers a new way to evaluate estrogen receptor activity, which is crucial for understanding how the cancer behaves. Unlike standard imaging techniques like CT or MRI, this method provides more detailed information about the presence and activity of estrogen receptors in recurrent or metastatic uterine cancer. This can potentially lead to more personalized treatment plans by identifying how well a cancer might respond to hormone therapies. Additionally, FES PET/CT could help in monitoring disease progression and treatment effectiveness more accurately than current options.

What evidence suggests that [18F]FES PET/CT imaging is effective for evaluating uterine cancer?

Research has shown that a special type of imaging called 18F-fluoroestradiol (FES) PET/CT can effectively detect estrogen receptor (ER) activity in patients with recurring or spreading uterine cancer. In this trial, participants with known or suspected recurrent or metastatic uterine cancer will undergo FES PET/CT imaging to evaluate ER activity. Studies have found that FES PET/CT can identify tumors that are ER-positive, which is important for understanding how the cancer might respond to hormone treatments. This imaging method is approved in the U.S. for use in cases where cancer has returned or spread, and it complements traditional biopsy methods. It offers a non-invasive way to see ER activity in the body, which can help guide treatment decisions. While FES PET/CT is mainly used for breast cancer, it can also be beneficial for assessing ER activity in uterine cancer. These findings suggest that FES PET/CT is a valuable tool for managing and understanding uterine cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Neil Taunk, MD

Principal Investigator

Abramson CC

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older with recurrent, metastatic, or untreated uterine cancer confirmed by biopsy or imaging. Participants must have at least one lesion outside the liver and cannot be pregnant. Those on tamoxifen or fulvestrant need a washout period before scanning. The study requires informed consent.

Inclusion Criteria

I have at least one cancer spot outside my liver, confirmed by scans.

I stopped taking tamoxifen or fulvestrant 8 or 28 weeks ago, respectively, before a FES PET/CT scan.

Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures

Exclusion Criteria

Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study

Females who report they are pregnant at screening will not be eligible for this study. A urine pregnancy test will be performed in women of child-bearing potential prior to FES injection

Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Imaging

Participants undergo the first FES PET/CT scan to evaluate estrogen receptor activity

1 day

1 visit (in-person)

Optional Second Imaging

Participants may undergo a second FES PET/CT scan at the time of disease progression to compare changes in FES uptake

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in FES uptake and progression-free survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Fluoroestradiol

Trial Overview [18F]Fluoroestradiol (FES) PET/CT scans are being tested to assess estrogen receptor activity in uterine cancer lesions. This may include initial scans before therapy and follow-up scans at disease progression to observe changes in FES uptake.

How Is the Trial Designed?

Group I: Recurrent or metastatic uterine cancer Experimental Treatment 1 Intervention

Women with known or suspected recurrent or metastatic uterine cancer may be eligible for this study. Patients may participate in this study if they are at least 18 years of age, most participants will be receiving care at the clinical practices of the University of Pennsylvania. \[18F\]fluoroestradiol (FES) PET/CT imaging will be used to evaluate estrogen receptor (ER) activity in areas of disease known by standard of care imaging (e.g. CT, MRI, Bone Scan, FDG PET/CT, ultrasound) or clinical exam. For patients starting a new line of therapy, imaging will occur prior to starting new therapy. For patients who completed an initial scan and are starting new therapy, some patients may also undergo a second FES PET/CT scan at the time of suspected progression of disease to compare for changes in FES uptake measures (prior to initiation of next line therapy).

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

The PET imaging agent [18F]16alpha-fluoroestradiol (FES) is effective for studying estrogen receptors in breast cancer, with a calculated effective dose equivalent of 0.022 mSv/MBq, indicating a low radiation exposure for patients.

The highest radiation dose was received by the liver, but overall, the radiation risks associated with FES imaging are comparable to other common nuclear medicine tests and are considered safe within accepted limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]fluoroestradiol radiation dosimetry in human PET studies. Mankoff, DA., Peterson, LM., Tewson, TJ., et al.[2016]

In a study of 16 patients with metastatic ER-positive breast cancer, the absence of estrogen receptor expression as measured by [18F]FES PET was a strong predictor of poor response to the treatment with rintodestrant, indicating that monitoring ER expression can guide treatment decisions.

The study found that [18F]FES uptake could effectively monitor the reversible effects of rintodestrant therapy, with no uptake in lesions during treatment suggesting a lack of response, while restoration of uptake after treatment indicated potential for continued therapeutic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant. Iqbal, R., Yaqub, M., Bektas, HO., et al.[2023]

In a study involving 33 breast cancer patients, (18)F-FES PET was found to significantly improve diagnostic understanding in 88% of cases and led to changes in therapy for 48% of patients, highlighting its potential as a valuable tool in clinical decision-making.

The (18)F-FES PET tracer was particularly effective in detecting bone metastases, identifying 341 lesions compared to 246 found through conventional imaging, although its sensitivity for liver metastases was limited due to high background activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma. van Kruchten, M., Glaudemans, AW., de Vries, EF., et al.[2016]

In gynecologic cancers, 18F-FES PET/CT imaging can help differentiate between malignant and benign uterine tumors, as higher uptake is associated with more aggressive cancers like endometrial carcinoma and uterine sarcoma.

For patients with platinum-resistant epithelial ovarian carcinoma, 18F-FES PET/CT can predict how well they will respond to antiestrogen therapy, highlighting its potential as a valuable tool in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-18F-2-Fluoro-2-Deoxy-d-Glucose PET/Computed Tomography in Gynecologic Oncology: An Overview of Current Status and Future Potential. Kalshetty, A., Basu, S.[2018]

16alpha-[(18)F]Fluoro-17beta-estradiol (FES) PET scans can noninvasively assess estrogen receptor expression in endometrial tissues, helping to differentiate between endometrial hyperplasia and carcinoma.

In two postmenopausal patients on tamoxifen, FES-PET and FDG-PET showed no abnormal tracer accumulation despite MRI suggesting carcinoma, highlighting the need to consider hormonal therapy's impact on FES accumulation when interpreting results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinctive FDG and FES accumulation pattern of two tamoxifen-treated patients with endometrial hyperplasia. Tsujikawa, T., Okazawa, H., Yoshida, Y., et al.[2016]

An improved automated synthesis of the PET tracer 18F-Fluoroestradiol ([18F]FES) has been developed, yielding high radiochemical purity (>99%) and demonstrating stability for up to 24 hours, making it a reliable option for clinical use.

Clinical PET imaging studies show that [18F]FES specifically targets estrogen receptor-positive (ER+) breast cancer tissues, providing clearer delineation of these regions compared to [18F]FDG, which indicates its potential for better predicting hormone therapy responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical production, stability studies and PET imaging with 16-alpha-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patients. Kumar, P., Mercer, J., Doerkson, C., et al.[2016]

18F-fluoroestradiol (18F-FES) is an FDA-approved radiopharmaceutical that enhances the molecular imaging of estrogen receptors in ER-positive breast cancer, particularly in metastatic cases.

The use of 18F-FES combined with PET imaging can aid in treatment selection and staging, as well as provide valuable insights into tumor heterogeneity and the specific imaging of lobular breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging for Estrogen Receptor-Positive Breast Cancer: Clinical Applications of Whole Body and Dedicated Breast Positron Emission Tomography. Goodman, K., Abel, MK., Lawhn-Heath, C., et al.[2023]

In a study of 19 women with newly diagnosed estrogen receptor-positive breast cancer, 18F-FES PET/CT demonstrated a higher sensitivity (90.8%) for detecting lesions compared to 18F-FDG PET/CT (82.8%), indicating its superior diagnostic capability.

The use of 18F-FES PET/CT led to a change in treatment management for 26.3% of patients, highlighting its potential to significantly influence clinical decisions in the management of ER-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FES PET/CT Influences the Staging and Management of Patients with Newly Diagnosed Estrogen Receptor-Positive Breast Cancer: A Retrospective Comparative Study with 18F-FDG PET/CT. Liu, C., Gong, C., Liu, S., et al.[2020]

In a study of 312 FES PET scans from 239 patients with ER+ primary breast cancer, sex hormone-binding globulin (SHBG) was found to inversely affect FES uptake, indicating its importance in assessing estrogen receptor expression.

The study suggests that FES uptake can be reliably measured by adjusting for lean body mass (LBM), and that pre-menopausal estradiol levels do not significantly impact FES uptake, allowing for simplified imaging protocols without compromising accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. Peterson, LM., Kurland, BF., Link, JM., et al.[2021]

18F-FDG PET is superior to conventional imaging for diagnosing gynecological cancers, particularly in detecting metastatic lesions and assessing treatment response, highlighting its efficacy in clinical settings.

18F-FES PET offers additional diagnostic and prognostic value for estrogen-related gynecological tumors beyond breast cancer, allowing for in vivo assessment of tumor behavior and heterogeneity, which can enhance treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging of Estrogen Receptors for Gynecological Tumors. Tsujikawa, T., Makino, A., Mori, T., et al.[2022]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08385

[18F] Fluoroestradiol PET/CT Imaging for the Detection of ... This study may help researchers learn whether 18F-FES PET/CT can detect estrogen receptor positive in patients with recurrent or metastatic uterine cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7886184/

Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as ... This study utilizes 18 F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5410246/

18F-FDG/18F-FES standardized uptake value ratio ... Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors ...

4. pubs.rsna.org pubs.rsna.org/doi/abs/10.1148/rg.220143

18F-Fluoroestradiol: Current Applications and Future ... Fluorine 18 fluoroestradiol (FES) PET/CT is approved in the United States as an adjunct to biopsy in patients with recurrent or metastatic ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/57/8/1269

18F-Fluoroestradiol PET: Current Status and Potential Future ... 18 F-FES PET has been evaluated in numerous breast cancer clinical studies as a promising method for quantifying in vivo ER expression, predicting response to ...

6. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/fes-ib.pdf

Investigator's Brochure [18F]Fluoroestradiol Safety and Toxicity of Other Components of Final [18F]FES Drug Product. The [18F]FES is purified by HPLC using an eluent of 50% ethanol USP in sterile water ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05916196/18ffes-pet-ct-in-uterine-cancer

[18F]FES PET/.CT in Uterine Cancer [18F]fluoroestradiol (FES) PET/CT imaging will be used to evaluate estrogen receptor (ER) activity in areas of disease known by standard of care ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05916196

NCT05916196 | [18F]FES PET/.CT in Uterine Cancer [18F]fluoroestradiol (FES) PET/CT imaging will be used to evaluate estrogen receptor (ER) activity in areas of disease known by standard of care imaging (e.g. ...