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

Trial Summary

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 data supports the effectiveness of the drug 18F-fluorofuranylnorprogesterone (18F-FFNP) in breast cancer treatment resistance?

Research shows that changes in tumor uptake of 18F-FFNP after an estradiol challenge can predict response to endocrine therapy in women with estrogen receptor-positive breast cancer, with 100% sensitivity and specificity, indicating its potential effectiveness in identifying patients who will benefit from such therapy. ^{1 2 3 4 5}

Is 18F-FFNP safe for use in humans?

The first-in-human study of 18F-FFNP was designed to evaluate its safety and dosimetry (measurement of radiation dose) for imaging progesterone receptors in breast cancer, indicating that safety assessments have been conducted. ^{1 3 4 6 7}

How does the treatment for breast cancer treatment resistance differ from other treatments?

This treatment is unique because it uses a PET-based estradiol challenge to predict the response to endocrine therapy by measuring changes in tumor progesterone receptor levels, which is not a standard approach in breast cancer treatment. ^{1 2 4 8 9}

What is the purpose of this trial?

This pilot observational study is being done to identify possible biomarkers of response to endocrine therapy in patients with ER/PR+ metastatic lobular breast cancer (LBC) starting new endocrine therapy. 18F-fluorofuranylnorprogesterone Positron Emission Tomography/Computed Tomography (FFNP-PET/CT) and liquid biopsies will be performed at baseline and after 4 weeks of treatment. Baseline levels and dynamic on-treatment changes in estrogen signaling as measured by FFNP-PET/CT and circulating tumor cell (CTC) liquid biopsy will be correlated with clinical response to endocrine therapy and progression-free survival in the above cohort of patients.

Research Team

Marina N. Sharifi

Principal Investigator

UW Carbone Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Novel methods and tracers for breast cancer imaging. [2013]

3. United States 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

The Development of 18F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1. [2023]

5. England 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. [2022]

6. Ireland 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. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Multimodal Approach to Outcome Prediction in Metastatic Castration-Resistant Prostate Cancer by Integrating Functional Imaging and Plasma DNA Analysis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Circulating tumor cells in breast cancer. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Circulating tumour DNA dynamics for assessment of molecular residual disease and for intercepting resistance in breast cancer. [2023]