Biomarkers to Detect Endocrine Therapy Resistance

Phase 2

Recruiting

• Conditions: Metastatic Cancer; Breast Cancer; Lobular Breast Carcinoma
• Interventions: Drug: 18F-fluorofuranylnorprogesterone; Device: Liquid Biopsy; Device: Positron Emission Tomography/Computed Tomography

• Registration Number: NCT06067503
• Lead Sponsor: University of Wisconsin, Madison

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-19
• Study First Submitted QC: 2023-09-27
• Study First Posted: 2023-10-05
• Study Start: 2024-04-30
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-16
• Last Update Posted: 2025-04-22
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. Willing to provide informed consent
2. Individuals at least 18 years of age
3. Have biopsy-proven ER/PR-positive (defined as ER ≥1 percent and PR ≥1 percent by IHC) and HER2-negative advanced or metastatic LBC starting new standard of care endocrine therapy
4. Adequate organ function as indicated by standard laboratory tests (CBC, liver function tests or CMP) allowing for systemic breast cancer treatment per treating oncologist
5. Patients with evaluable bone-only disease that is lytic or mixed lytic-sclerotic are eligible
6. Willing to comply with all study procedures and be available for the duration of the study
7. Disease may be measurable by RECIST 1.1 criteria or non-measurable. Lesion size must be at least 1cm. If only bone lesions present, they should be lytic or mixed lytic-sclerotic. If only liver lesions present, patient is not eligible.

Exclusion Criteria

1. Patients with active brain metastases
2. Patients with liver-only disease are not eligible due to high background liver activity related to the radiopharmaceutical's hepatobiliary route of elimination
3. Unable to lie flat during or tolerate PET/CT
4. Patients with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP
5. Presence of liver failure as judged by patient's treating physician
6. Individuals who are pregnant, lactating, or planning on becoming pregnant during the study
7. Not suitable for study participation due to other reasons at the discretion of the investigators
8. Patients with progesterone-receptor negative disease defined as PR <1 percent by IHC

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants with ER/PR+ metastatic lobular breast cancer (LBC)	18F-fluorofuranylnorprogesterone	-
Participants with ER/PR+ metastatic lobular breast cancer (LBC)	Liquid Biopsy	-
Participants with ER/PR+ metastatic lobular breast cancer (LBC)	Positron Emission Tomography/Computed Tomography	-

Primary Outcome Measures

Name	Time	Method
Number of Participants who have decreased FFNP uptake on PET/CT in response to endocrine therapy	baseline, 4 weeks
Number of Participants who have decrease in circulating tumor cell estrogen signaling in response to endocrine therapy	baseline, 4 weeks	Baseline level and on-treatment CTC ESR1 and estrogen regulated gene expression will be evaluated as well as endocrine-resistance associated mutations including ESR1 (though rare in this patient population) and PGR.
Number of Participants who have a decrease in concentration of Circulating Tumor DNA in response to endocrine therapy	baseline, 4 weeks

Secondary Outcome Measures

Name	Time	Method
Adverse Events within 24 hours of FFNP infusion	a 24 hour period up to 7 days pre-treatment, a 24 hour period 4 weeks after the first infusion
Progression Free Survival (PFS) for 6 months	up to 6 months
Correlation coefficients	up to 6 months	Correlate baseline levels and dynamic on treatment changes in estrogen signaling as measured by FFNP-PET/CT and CTC liquid biopsy with clinical response to endocrine therapy and progression-free survival in patients with ER/PR+ metastatic LBC.

Trial Locations

Locations (1)

UW Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States