Biomarker Testing for Breast Cancer Treatment Resistance

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must be taking: Endocrine therapy

Disqualifiers: Brain metastases, Liver-only disease, 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: 3

Duration: 4 weeks

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain biomarkers (substances in the body that can indicate disease) can predict the response of patients with ER/PR+ metastatic lobular breast cancer to endocrine therapy. By using advanced imaging, such as Positron Emission Tomography/Computed Tomography (PET/CT), and blood tests like the Liquid Biopsy, researchers aim to determine if changes in these biomarkers reveal how the cancer reacts to treatment. The trial seeks participants diagnosed with this specific type of breast cancer who are starting a new standard endocrine therapy. Participants must have cancer not located in the liver and be able to undergo imaging tests. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What prior data suggests that this protocol is safe for patients with ER/PR+ metastatic lobular breast cancer?

A previous study demonstrated that a substance called 18F-FFNP safely images breast cancer, with no reported side effects, indicating good patient tolerance. Liquid biopsies, which test blood samples for cancer cells or DNA, are safe and enhance doctors' understanding of cancer without requiring surgery. PET/CT scans, commonly used to examine the body, are generally safe and offer crucial insights into cancer behavior. Overall, past research has shown the methods used in this study to be safe, with no strong evidence of harmful side effects, making them promising options for patients considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer a fresh approach to tackling resistance in breast cancer treatment. Unlike standard therapies that often focus solely on hormone receptor blocking or chemotherapy, this trial uses advanced biomarker testing and imaging techniques to understand and predict treatment resistance. The use of 18F-fluorofuranylnorprogesterone and liquid biopsies, combined with Positron Emission Tomography/Computed Tomography (PET/CT), is particularly innovative. This combination allows for precise tracking of how breast cancer cells respond to treatments in real-time, potentially leading to more personalized and effective treatment plans.

What evidence suggests that this trial's treatments could be effective for breast cancer?

In this trial, participants with ER/PR+ metastatic lobular breast cancer will undergo testing with a special imaging technique using a substance called 18F-FFNP. Research has shown that this technique, involving PET/CT scans, can identify breast cancers likely to respond well to anti-estrogen treatments by measuring the progesterone receptor protein in the cancer. Additionally, the trial will use liquid biopsies to examine tumor cells or DNA in the blood. Studies indicate that liquid biopsies can predict treatment effectiveness and monitor any resistance the cancer may develop. Both methods offer promising ways to better understand and manage breast cancer treatment resistance. ^{4 6 7 8 9}

Who Is on the Research Team?

Marina N. Sharifi

Principal Investigator

UW Carbone Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with ER/PR+ metastatic lobular breast cancer who are starting new endocrine therapy. They must have adequate organ function, lesions of at least 1cm (or specific bone lesions), and not just liver disease. Pregnant individuals or those with brain metastases, liver failure, allergies to similar compounds as FFNP, or progesterone-receptor negative disease cannot participate.

Inclusion Criteria

My cancer can be measured or not, but if only in bones, they are lytic or mixed. No liver-only lesions.

My blood and liver tests are good enough for cancer treatment.

I am willing and able to follow all study rules and attend all appointments.

Exclusion Criteria

I have active cancer spread to my brain.

My cancer has not spread only to my liver.

My doctor has diagnosed me with liver failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline FFNP-PET/CT and liquid biopsies are performed to measure estrogen signaling

1 week

1 visit (in-person)

Treatment

Participants receive new endocrine therapy and undergo FFNP-PET/CT and liquid biopsies after 4 weeks

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for clinical response and progression-free survival

up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• 18F-fluorofuranylnorprogesterone
• Liquid Biopsy
• Positron Emission Tomography/Computed Tomography

Trial Overview The study aims to find biomarkers predicting the response to endocrine therapy in patients using two methods: FFNP-PET/CT scans and liquid biopsies before and after four weeks of treatment. The results will be linked to how well the therapy works and how long patients live without their cancer getting worse.

How Is the Trial Designed?

Group I: Participants with ER/PR+ metastatic lobular breast cancer (LBC) Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

A meta-analysis of 11 studies involving 327 lesions showed that 18F-FES PET imaging has a sensitivity of 81% and specificity of 86% for assessing estrogen receptor status in metastatic breast cancer, indicating its effectiveness as a non-invasive diagnostic tool.

18F-FES PET could complement traditional tissue assays for determining ER status, potentially improving treatment decisions and outcomes for patients with metastatic breast cancer, especially in cases with brain metastases or lobular histology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-Body Characterization of Estrogen Receptor Status in Metastatic Breast Cancer with 16α-18F-Fluoro-17β-Estradiol Positron Emission Tomography: Meta-Analysis and Recommendations for Integration into Clinical Applications. Kurland, BF., Wiggins, JR., Coche, A., et al.[2022]

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]

In a study of 105 patients with metastatic castration-resistant prostate cancer (mCRPC), higher levels of androgen receptor (AR) copy number in plasma DNA were significantly associated with worse progression-free and overall survival, indicating its potential as a biomarker for treatment personalization.

The integration of 18F-fluorocholine (FCH) PET/CT imaging with plasma AR analysis and other circulating biomarkers (like LDH and NLR) showed promise in predicting patient outcomes, suggesting that combining these methods could enhance treatment selection strategies for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Approach to Outcome Prediction in Metastatic Castration-Resistant Prostate Cancer by Integrating Functional Imaging and Plasma DNA Analysis. Conteduca, V., Scarpi, E., Matteucci, F., et al.[2022]

The development of the PET radiotracer 18F-FTT for imaging PARP-1 has progressed from preclinical evaluation to first-in-human studies, showing promise as a biomarker for measuring PARP-1 levels in breast and ovarian cancer patients.

The article outlines the regulatory process for submitting an investigational new drug application to the FDA and emphasizes the need for a commercialization strategy to facilitate multicenter clinical trials for future approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Development of 18F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1. Lee, HS., Schwarz, SW., Schubert, EK., et al.[2023]

Circulating tumor DNA (ctDNA) monitoring shows promise in identifying breast cancer patients at higher risk of relapse, with several studies supporting its clinical validity for assessing molecular residual disease (MRD).

The PADA-1 trial is the only study so far to demonstrate the clinical utility of ctDNA dynamics in improving progression-free survival, highlighting the need for more rigorous trials to confirm its effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumour DNA dynamics for assessment of molecular residual disease and for intercepting resistance in breast cancer. Valenza, C., Trapani, D., Curigliano, G.[2023]

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 43 postmenopausal women with advanced ER+ breast cancer, a one-day estradiol challenge significantly increased tumor uptake of the progestin analog FFNP in those who responded to endocrine therapy, indicating a strong predictive relationship (100% sensitivity and specificity).

The study found that responders to endocrine therapy not only showed increased FFNP uptake but also experienced significantly longer survival compared to nonresponders, highlighting the potential of this method to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy. Dehdashti, F., Wu, N., Ma, CX., et al.[2021]

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]

Circulating tumor cell (CTC) detection methods have become reliable over the past decade, allowing for the collection of significant data on CTC counts in cancer patients, particularly in breast cancer.

CTC counts have been validated as a dynamic prognostic biomarker in both early and metastatic breast cancer, providing insights into cancer biology and metastasis through molecular characterization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor cells in breast cancer. Bidard, FC., Proudhon, C., Pierga, JY.[2021]

Citations

1. withpower.com withpower.com/trial/phase-2-breast-neoplasms-2024-f9213

Biomarker Testing for Breast Cancer Treatment Resistance What data supports the effectiveness of the drug 18F-fluorofuranylnorprogesterone (18F-FFNP) in breast cancer treatment resistance? Research shows that ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-07104

Using 18F-FFNP PET/CT and Minimally Invasive ... Using 18F-FFNP PET/CT and minimally invasive biomarkers may help to predict whether a cancer is sensitive to anti-estrogen treatment, a standard type of ...

3. radiology.wisc.edu radiology.wisc.edu/research-projects/18ffluorofuranylnorprogesterone-ffnp-petmr-imaging-of-progesterone-receptor-expression-in-invasive-breast-cancer/

[18F]Fluorofuranylnorprogesterone (FFNP) PET/MR ... In this study, a PET tracer called FFNP that binds to the progesterone receptor is used to visualize the level of PR present, which is also indicative of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8049349/

Head-to-Head Evaluation of 18F-FES and 18F-FDG PET ... Methods: Six prospective clinical trials using 18F-FES PET/CT in patients with metastatic breast cancer were performed at Memorial Sloan Kettering Cancer Center ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950195425000281

Liquid biopsy in breast cancer: Redefining precision ... Moreover, under treatment pressure, tumor cells may undergo molecular changes and phenotypic plasticity, leading to resistance and therapeutic failure. Although ...

6. 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 ...

7. 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 ...

8. 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 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11205053/

PET Molecular Imaging in Breast Cancer: Current Applications ... This review addresses the role of PET imaging in breast cancer care. We focus primarily on the utility of 18F-fluorodeoxyglucose (FDG) PET in staging, ...