Biomarkers to Detect Endocrine Therapy Resistance
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Wisconsin, Madison
About 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Willing to provide informed consent
Individuals at least 18 years of age
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
Adequate organ function as indicated by standard laboratory tests (CBC, liver function tests or CMP) allowing for systemic breast cancer treatment per treating oncologist
Disqualifiers
Patients with active brain metastases
Patients with liver-only disease are not eligible due to high background liver activity related to the radiopharmaceutical's hepatobiliary route of elimination
Unable to lie flat during or tolerate PET/CT
Patients with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to FFNP
Trial design
Design model
Single group
Treatments tested in this trial
18F-fluorofuranylnorprogesterone
DrugThe dose of the investigational imaging agent, FFNP, is approximately 7 millicurie (mCi) (259 megabecquerels (MBq)), IV slow infusion over approximately two minutes followed by saline flush.
Liquid Biopsy
Device20ml of whole blood will be collected into two Ethylenediaminetetraacetic acid (EDTA) tubes at each timepoint, CTCs are isolated using the microfluidic Versatile Exclusion-based Rare Sample Analysis (VERSA) platform that integrates CTC capture with RNA extraction on a single chip using Exclusion-Based Sample Preparation (ESP) technology
Positron Emission Tomography/Computed Tomography
DeviceFFNP drug in combination with PET/CT scans to image participant
Treatment groups
8 Participants
are divided into 1 treatment groupGroup A: Participants with ER/PR+ metastatic lobular breast cancer (LBC)Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Number of Participants who have decreased FFNP uptake on PET/CT in response to endocrine therapy
Time frame
baseline, 4 weeks2
Number of Participants who have decrease in circulating tumor cell estrogen signaling in response to endocrine therapy
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.
Time frame
baseline, 4 weeks3
Number of Participants who have a decrease in concentration of Circulating Tumor DNA in response to endocrine therapy
Time frame
baseline, 4 weeksSecondary outcomes
1
Progression Free Survival (PFS) for 6 months
Time frame
up to 6 months2
Correlation coefficients
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.
Time frame
up to 6 months3
Adverse Events within 24 hours of FFNP infusion
Time frame
a 24 hour period up to 7 days pre-treatment, a 24 hour period 4 weeks after the first infusionSponsors and contacts
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Source ClinicalTrials.gov