FFNP PET/MRI for Endometrial Cancer

Overseen By Louis Murphy

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Levonorgestrel IUD

Disqualifiers: Claustrophobia, Metallic implants, Pregnancy, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special scan, called FFNP PET/MRI (18F-fluorofuranylnorprogesterone PET/MRI), can predict the effectiveness of a Levonorgestrel-releasing Intrauterine Device (LR-IUD) for women with Complex Atypical Hyperplasia (CAH) or early-stage Endometrial Cancer (EC). The trial includes one scan and monitors medical records for six months to assess treatment response. Women who have not undergone surgery or hormonal treatment for these conditions and plan to use the LR-IUD may be suitable candidates. Participants should not have severe claustrophobia or certain metal implants and must be able to complete the scan.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that participants should not have had prior hormonal treatment for CAH or Grade 1 EC.

What prior data suggests that FFNP PET/MRI is safe for predicting response to hormonal therapy in endometrial cancer?

Research has shown that 18F-fluorofuranylnorprogesterone (FFNP) PET/MRI has been tested in people. In one study with 20 patients, this imaging method proved safe, with no major safety issues reported. Participants tolerated the procedure well.

Other studies have used FFNP to examine hormone receptors in the body, aiding doctors in understanding hormone functions. Importantly, this imaging tool successfully passed at least one previous human trial, indicating its safety for use in people.

For those considering joining a trial with FFNP PET/MRI, current evidence supports its safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 18F-fluorofuranylnorprogesterone PET/MRI because it offers a novel approach to diagnosing and evaluating endometrial cancer. Unlike traditional imaging techniques, this method uses a specialized tracer that targets progesterone receptors, potentially providing more precise and detailed images of the cancer. This innovative technique could enhance the accuracy of cancer staging and treatment planning, leading to better outcomes for patients.

What evidence suggests that FFNP PET/MRI is effective for predicting response to LR-IUD hormonal therapy for CAH and EC?

Research shows that a special type of scan called FFNP PET/MRI effectively detects progesterone receptors, which play a role in some cancers, such as breast cancer. This scan is more accurate and sensitive than other imaging methods. Studies have found that PET/MRI is particularly useful for accurately identifying the stage of endometrial cancer, especially in its early stages. Previous research confirmed that FFNP PET imaging is safe and effective, with no harmful effects reported. This imaging technique can also help predict the effectiveness of treatments like the Levonorgestrel-releasing Intrauterine Device (LR-IUD) for conditions such as complex atypical hyperplasia and endometrial cancer. In this trial, all enrolled subjects will receive the FFNP tracer and then undergo a PET/MRI scan to evaluate its effectiveness in staging endometrial cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Jorge Oldan, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older with confirmed Complex Atypical Hyperplasia (CAH) or Grade 1 Endometrial Cancer (EC), who are planning to be treated with a Levonorgestrel-releasing Intrauterine Device (LR-IUD). Participants should not have had previous surgical or hormonal treatments for these conditions. Women with certain metal implants, allergies to gadolinium or FFNP, severe kidney issues, pregnancy, prior hormone treatment for breast cancer, or extreme claustrophobia cannot join.

Inclusion Criteria

I am planning to use an IUD for my uterine condition.

My condition is confirmed as CAH or Grade 1 endometrial cancer.

I have not had surgery or hormone treatment for CAH or early-stage endometrial cancer.

Exclusion Criteria

Inability to complete PET/MR scans due to severe claustrophobia

Implanted metallic devices, parts, vascular clips, or other foreign bodies

I am not pregnant, confirmed by a recent test or my medical history.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants receive one FFNP PET/MRI scan to establish baseline measurements

1 day

1 visit (in-person)

Treatment

Participants undergo treatment with Levonorgestrel-releasing Intrauterine Device (LR-IUD) and are monitored for response

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-fluorofuranylnorprogesterone PET / MRI

Trial Overview The study is testing the effectiveness of an imaging scan called FFNP PET/MRI in predicting how well CAH and EC respond to hormonal therapy via LR-IUD. It's a small-scale pilot study involving eight participants who will undergo one FFNP PET/MRI scan each and have their medical records reviewed over six months.

How Is the Trial Designed?

Group I: 18F-fluorofuranylnorprogesterone PET / MRI Experimental Treatment 1 Intervention

All enrolled subjects will receive the tracer and then have a PET/MRI scan.

18F-fluorofuranylnorprogesterone PET / MRI is already approved in United States, European Union for the following indications:

Approved in United States as FFNP PET/MRI for:

• Research use only, not approved for clinical use

Approved in European Union as FFNP PET/MRI for:

• Research use only, not approved for clinical use

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Radiological Society of North America

Collaborator

Trials

27

Recruited

1,000+

Published Research Related to This Trial

The study identified 21-fluoro-16 alpha-methyl-19-norprogesterone ([18F]FMNP) as a promising imaging agent for detecting progesterone receptor positive tumors, showing high specificity and minimal binding to other steroid receptors.

In vivo tests in rats demonstrated that [18F]FMNP had significantly higher uptake in uterine and tumor tissues compared to blood, correlating strongly with progesterone receptor concentrations, indicating its potential for effective imaging of progesterone receptor positive neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of a positron emitting progestin ([18F]fluoro-16 alpha-methyl-19-norprogesterone) for imaging progesterone receptor positive tumours with positron emission tomography. Verhagen, A., Luurtsema, G., Pesser, JW., et al.[2019]

The study demonstrated that (18)F-FFNP PET is a safe and effective method for imaging progesterone receptors in breast cancer, with no adverse effects reported in 20 patients.

While the maximum uptake of (18)F-FFNP was similar in both PR-positive and PR-negative tumors, the tumor-to-normal breast activity ratio was significantly higher in PR-positive cancers, indicating better imaging potential for these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of progesterone receptors in breast carcinoma by PET with 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione. Dehdashti, F., Laforest, R., Gao, F., et al.[2021]

In a study of 33 patients with biopsy-proven endometrial cancer, MRI using an endorectal coil (eMRI) demonstrated a staging accuracy of 71%, particularly excelling in assessing myometrial invasion with 75% accuracy for stage T1a and 80% for stage T1b.

Despite its promising results, eMRI at 1.5T did not show significant accuracy improvements over standard pelvic MRI for staging endometrial cancer, suggesting it may not be as beneficial as previously hoped based on its success in prostate cancer staging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accuracy of MRI with an endorectal coil for staging endometrial cancer. Alt, CD., Brocker, KA., Eichbaum, M., et al.[2012]

PET/MR imaging provides enhanced soft tissue contrast and better evaluation of primary tumors in gynecologic cancers, particularly cervical, endometrial, and ovarian cancers.

The integration of functional MR techniques, like diffusion-weighted imaging, with PET/MR imaging represents a significant advancement in multimodal imaging, potentially improving the management and treatment planning for patients with these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emerging Role of PET/MR Imaging in Gynecologic Cancers. Ponisio, MR., Fowler, KJ., Dehdashti, F.[2017]

Endometrial cancer, the second most common gynecological cancer, is often diagnosed early due to symptoms like post-menopausal bleeding, which increases the chances of successful treatment.

Magnetic resonance imaging (MRI) plays a crucial role in determining the stage of endometrial cancer, aiding in the decision-making process for treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR staging of endometrial carcinoma. Messiou, C., Spencer, JA., Swift, SE.[2006]

Non-contrast 18F-FDG PET/MRI demonstrated a high diagnostic accuracy for assessing the primary tumor in endometrial cancer, with an accuracy of 77.8%, comparable to contrast-enhanced MRI (75.0%).

For detecting regional nodal metastasis, 18F-FDG PET/MRI showed superior sensitivity (100%) compared to contrast-enhanced CT (14.3%), indicating its potential as a more effective diagnostic tool in preoperative staging of endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value of 18F-FDG PET/MRI for staging in patients with endometrial cancer. Tsuyoshi, H., Tsujikawa, T., Yamada, S., et al.[2020]

(18)F-FDG PET imaging shows high specificity (89.8%) for detecting primary endometrial cancer lesions, but its sensitivity (81.8%) is relatively low, limiting its effectiveness for initial tumor detection.

The imaging technique is particularly effective for identifying distant metastases, with a sensitivity of 95.7% and specificity of 95.4%, indicating it is a reliable tool for assessing advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of fluorine 18 fluorodeoxyglucose positron emission tomography imaging for detection of primary lesion and staging of endometrial cancer patients: systematic review and meta-analysis of the literature. Kakhki, VR., Shahriari, S., Treglia, G., et al.[2022]

In a study of 62 endometrial cancer patients, higher levels of 18F-FDG uptake (measured as SUVmax) were associated with negative estrogen receptor (ER) and progestogen receptor (PR) expression, indicating that lower SUVmax values may suggest a better response to progestogen therapy.

The study found that 18F-FDG PET/CT can accurately predict ER and PR status with an accuracy of 74.2%, which could help guide treatment decisions for patients with endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between the expression of oestrogen receptor and progesterone receptor and 18F-FDG uptake in endometrial cancer. Wu, C., Chen, R., Xu, L., et al.[2021]

Magnetic resonance imaging (MRI), especially contrast-enhanced MRI, is the preferred imaging method for diagnosing endometrial carcinoma, the most common gynecological cancer in developed countries.

Novel MRI techniques, such as diffusion-weighted MRI, can improve the detection of malignant lesions and assess the extent of myometrial invasion, potentially leading to more accurate diagnoses and better treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Staging of endometrial carcinomas with MRI using traditional and novel MRI techniques. Haldorsen, IS., Salvesen, HB.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05483023

18-fluorofuranylnorprogesterone (FFNP) PET/MRI as a ... Purpose: The purpose of this study is to evaluate FFNP PET/MRI's utility for predicting response to Levonorgestrel-releasing Intrauterine Device (LR-IUD) ...

2. withpower.com withpower.com/trial/phase-2-endometrial-cancer-8-2022-6c26b

FFNP PET/MRI for Endometrial Cancer · Info for Participants The study demonstrated that (18)F-FFNP PET is a safe and effective method for imaging progesterone receptors in breast cancer, with no adverse effects reported ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9858166/

Current Update on PET/MRI in Gynecological ... The combined PET/CT was studied, which showed high sensitivity (91% vs. 37.3%) and diagnostic accuracy (98% vs. 95%) compared to MRI (p < 0.034) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9438318/

Diagnostic value of integrated 18F-FDG PET/MRI for ... PET/MRI had a higher accuracy for the staging of endometrial carcinoma, mainly for FIGO stage I tumors compared to PET/CT.

5. jnm.snmjournals.org jnm.snmjournals.org/content/60/2/220

Sensitivity and Isoform Specificity of 18F ... One study of 20 patients has been published, to date, demonstrating the safety, dosimetry, and ability of 18F-FFNP PET imaging for identifying ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7465097/

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen ... This review covers our development of three PET imaging agents, 16α-[ 18 F]fluoroestradiol (FES) for ER, 21-[ 18 F]fluoro-furanyl-nor-progesterone (FFNP) for ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/542097

Evaluation of Endometriosis With 18F ... Purpose: The aim of this study is to assess the sensitivity and specificity of FFNP PET/MRI for diagnosis of endometriosis.