18F-FFNP PET/MRI for Breast Cancer

Overseen By Cancer Connect

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must not be taking: Aromatase inhibitors, ER antagonists

Disqualifiers: HER2-positive, Neoadjuvant therapy, Pregnant, 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

Compensation: Varies

Number of Visits: 4

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to predict how well breast cancer patients respond to hormone therapy before surgery. The treatment uses a special scan called 18F-FFNP PET/MRI (Positron Emission Tomography / Magnetic Resonance Imaging) to examine the progesterone receptor in the cancer. Women who have undergone menopause, have a specific type of breast cancer, and have not started certain cancer treatments might be suitable candidates. Participants may join different groups, such as those undergoing blood tests during scans or those having scans before and after taking anastrozole. 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 advancements in breast cancer care.

Will I have to stop taking my current medications?

If you are taking hormone replacement therapy or any over-the-counter products or supplements with potential estrogenic effects, you will need to stop taking them during the study until surgery. If you are currently taking aromatase inhibitors or ER antagonists like tamoxifen or raloxifene, you cannot participate in the trial.

What prior data suggests that 18F-FFNP PET/MRI is safe for breast cancer patients?

Research has shown that 18F-FFNP PET safely images progesterone receptors in breast cancer. In studies, 18F-FFNP caused no harmful effects in participants, indicating it was well-tolerated. The PET/MRI scan, which combines two imaging techniques, is also considered safe for evaluating breast cancer. Despite its advanced technology, it has been used in many studies without major safety concerns. In summary, previous research has demonstrated that both 18F-FFNP and PET/MRI are safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores an advanced imaging technique using 18F-fluorofuranylnorprogesterone (18F-FFNP) PET/MRI for breast cancer. Unlike traditional imaging methods, this technique allows for a more detailed view of how breast cancer behaves at the molecular level, potentially leading to more personalized treatment plans. The trial includes a unique approach with different groups: one focuses on analyzing metabolites through blood samples, another examines the effectiveness of pre-surgical treatment with anastrozole using before-and-after imaging, and a third tests the repeatability of the imaging technique. These innovative methods could significantly enhance our understanding and management of breast cancer, offering hope for more effective interventions in the future.

What evidence suggests that 18F-FFNP PET/MRI is effective for predicting response to endocrine therapy in breast cancer?

Research has shown that a special imaging method called 18F-FFNP effectively views progesterone receptors in breast cancer. This trial will explore the use of 18F-FFNP PET/MRI in different contexts. Participants in Group 1 will undergo venous blood sampling during the PET/MRI scan for metabolite analysis. Group 2 participants will have PET/MRI scans before and after two weeks of treatment with anastrozole to assess pre-surgical treatment effects. Group 3 will focus on test-retest reliability by having baseline and repeat PET/MRI scans without intervening treatment. Previous studies found that using 18F-FFNP with PET/MRI scans is safe and has no reported side effects. It can also detect changes in progesterone receptor levels when estrogen levels change, which is important for understanding treatment effectiveness. Overall, 18F-FFNP PET/MRI is a promising tool for evaluating breast cancer treatment outcomes. ^{1 2 4 5 6}

Who Is on the Research Team?

Amy M. Fowler

Principal Investigator

UW Carbone Cancer Center

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with newly diagnosed ER+/PR+/HER2- primary breast cancer, who haven't had any neoadjuvant therapy and are planning surgery. They must be able to lie prone for imaging, not have allergies to the study drugs or MRI contrast agents, and can't be on hormone replacement therapy.

Inclusion Criteria

My breast cancer is confirmed by biopsy and is at least 1.0 cm big.

My breast cancer is ER and PR positive but HER2 negative.

I am scheduled for or have had a breast MRI before surgery.

Exclusion Criteria

We need to have slides or tissue samples from your breast biopsy for testing, and if we don't have them, you can't participate in the study.

I have finished all initial treatments for my current cancer.

I don't need sedation for scans but can take mild anxiety medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-surgical Treatment

Participants undergo PET/MRI scans before and after 2 weeks of treatment with anastrozole

2 weeks

2 visits (in-person)

Test-Retest

Participants undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability

up to 6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 7 weeks

Long-term Follow-up

Statistical correlation between tumor 18F-FFNP uptake with disease recurrence

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• 18F-fluorofuranylnorprogesterone
• Positron Emissions Tomography / Magnetic Resonance Imaging

Trial Overview The trial tests if a PET/MRI scan using a tracer called 18F-FFNP can predict how well endocrine therapy will work before surgery in breast cancer patients. It also checks the reliability of this method. Participants will undergo blood sampling and receive Gadobenate dimeglumine and Anastrozole.

How Is the Trial Designed?

Group I: Group 3: Test-Retest Experimental Treatment 3 Interventions

participants will undergo baseline and repeat PET/MRI scans without intervening treatment to determine repeatability

Group II: Group 2: Pre-surgical Treatment Experimental Treatment 4 Interventions

participants will undergo PET/MRI scans before and after 2 weeks treatment with anastrozole

Group III: Group 1: Metabolite Analysis Experimental Treatment 4 Interventions

participants will undergo venous blood sampling during the PET/MRI scan

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

Novel PET tracers, such as FES and FFNP, are being developed to measure estrogen and progesterone receptor density in breast cancer, which can help in selecting targeted therapies.

These investigational tracers are advancing towards clinical use and may significantly improve the characterization of breast cancer biology, enhancing the ability to monitor treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel methods and tracers for breast cancer imaging. Linden, HM., Dehdashti, F.[2013]

6 alpha-[18F]fluoroprogesterone shows a relative binding affinity to progesterone receptors (PgR) that is comparable to progesterone, making it a potential imaging agent for PgR-positive breast cancer.

However, in vivo studies indicate that it has low target tissue selectivity and high fat uptake, suggesting that the C-6 position may not be ideal for fluorine-18 labeling in steroid imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

6 alpha-[18F]fluoroprogesterone: synthesis via halofluorination-oxidation, receptor binding and tissue distribution. Choe, YS., Bonasera, TA., Chi, DY., 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]

PET imaging agents like 16α-[18F]fluoroestradiol (FES), 21-[18F]fluoro-furanyl-nor-progesterone (FFNP), and 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) can help predict how well patients with breast and prostate cancers will respond to endocrine therapies by visualizing hormone receptors.

The development of these imaging agents reflects a growing understanding of the importance of receptor targeting in cancer treatment, potentially improving clinical management by identifying which patients are more likely to benefit from hormone-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging. Katzenellenbogen, JA.[2023]

A new fluorine-18 labeled analogue of Tanaproget, designed for imaging progesterone receptors (PRs) in breast tumors, shows high uptake in target tissues, indicating its potential effectiveness for positron emission tomography (PET) imaging.

The compound demonstrated excellent selectivity and prolonged retention in tissues, with significant differences in uptake between target tissues and blood, suggesting it could be a valuable tool for guiding endocrine therapy in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [F-18]fluorine-substituted Tanaproget as a progesterone receptor imaging agent for positron emission tomography. Lee, JH., Zhou, HB., Dence, CS., et al.[2015]

The study demonstrated that 18F-FFNP can effectively measure changes in progesterone receptor (PR) levels in response to estradiol treatment in both human breast cancer cells and tumor xenografts, with significant increases in uptake observed after 48 and 72 hours of treatment.

Importantly, 18F-FFNP showed equivalent binding to both PR isoforms (A and B), indicating its potential as a reliable imaging agent for assessing total PR expression in breast cancer without bias towards specific isoforms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity and Isoform Specificity of 18F-Fluorofuranylnorprogesterone for Measuring Progesterone Receptor Protein Response to Estradiol Challenge in Breast Cancer. Salem, K., Kumar, M., Yan, Y., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06086704

NCT06086704 | Study of 18F-FFNP Breast PET/MRI The overall purpose of this research is to test the efficacy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy and to determine the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8833853/

Sensitivity and Isoform Specificity of 18F- ... The purpose of this study was to evaluate the ability of 18F-FFNP to measure alterations in PR protein level and isoform expression in response to estradiol ...

3. withpower.com withpower.com/trial/phase-2-breast-neoplasms-2024-052ff

18F-FFNP PET/MRI for Breast Cancer 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 ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08594

18F-FFNP PET/MRI for the Assessment of Early Response ... This trial may help doctors find out if 18F-FFNP PET/MRI can help determine which tumors will respond best to endocrine therapy given before surgery, such as ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6651117/

Fluorine-18 Labeled Fluorofuranylnorprogesterone ([18F ... The overall yield of [ 18 F]FFNP was 64–72% (decay corrected) in 40 min synthesis time with a molar activity of 37–81 GBq/μmol (1000–2200 Ci/mmol).

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

Sensitivity and Isoform Specificity of 18F ... The purpose of this study was to evaluate the ability of 18F-FFNP to measure alterations in PR protein level and isoform expression in response ...