About this trial

Despite broad advancements in endocrine therapy for ERα+ breast cancer, resistance ultimately develops. A common driver of resistance are known ESR1 mutations that lead to constitutively active receptor signaling and transcriptional regulation that is always "turned on" despite the absence of estrogen. Patients with ESR1 mutations are expected to have decreased binding affinity for tamoxifen and thus may be underdosed on standard therapy. \[18F\]-fluoroestradiol Positron Emission Tomography/Computed tomography (FES-PET/CT) imaging is a novel functional imaging technique that can non-invasively measure ERα expression and inhibition in metastatic ERα+ breast cancer. The proposed a pilot study uses FES-PET/CT imaging to measure ERα blockade to determine the optimal dose of tamoxifen in patients with ESR1 mutations.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Estrogen receptor expression by immunohistochemistry greater than or equal to 10%

ESR1 mutation identified using a Clinical Laboratory Improvement Amendments (CLIA) certified assay via tumor biopsy tissue or circulating free DNA (cfDNA)

human epidermal growth factor receptor 2 (HER2) negative

Participants must have measurable disease as defined by RECIST 1.1 or evaluable bone disease with at least one lesion measuring 10 mm or greater in size. (Participants with bone and non-bone disease are eligible. One disease site must meet either the measurable or evaluable criteria outlined.) Participants with liver-only disease are not eligible due to the inherent hepatic uptake related to the radiopharmaceutical's hepatobiliary route of elimination.

Disqualifiers

Prior chemotherapy, radiotherapy, targeted, immunotherapy or investigational therapy within 2 weeks or major surgery within 4 weeks of study enrollment or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events due to agents administered more than 2 weeks earlier (alopecia and fatigue excluded).

Participants must not be receiving an ER blocking endocrine therapy (includes fulvestrant, tamoxifen, toremifene, raloxifene) and must be off the agents for a minimum of 60 days prior to planned FES PET/CT to allow for adequate uptake of FES.

History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of tamoxifen or [18F]-fluoroestradiol.

Peripheral neuropathy of severity greater than grade 1.

Trial design

Design model

Single group

Treatments tested in this trial

Tamoxifen
Drug
estrogen modulator
FES PET/CT
Diagnostic test
Radiolabeled estrogen \[18F\]-fluoroestradiol (FES) in combination with Positron Emission Tomography / Computed Tomography is a molecular imaging technique for measuring pharmacodynamic effects of endocrine therapy. The injected dose of 18F-FES will be 6 mCi (185 MBq) ± 20% with a specific activity greater than 170 Ci/mmol at the time of injection for an activity dose of 6 mCi. Participant will receive baseline imaging and repeat imaging after 3-4 weeks to evaluate for FES blockade as assigned dose level.

Treatment groups

12 Participants

are divided into 1 treatment group

Group A: Tamoxifen Dose LevelsExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Rate of FES Blockade at each dose level to determine the Optimal Tamoxifen Dose

Reduction in FES uptake will be described and analyzed by Fisher's exact test. Rates or proportion of responses at each dose level will be provided in data listings. If the SUVmax for all 5 target lesions have decreased by \> 75% or all 5 lesions have SUVmax\<1.5 on the second scan, then these participants will be prospectively defined as having complete FES blockade. If the SUVmax for any of the 5 lesions has not decreased by \> 75% or if any new lesions arise with SUVmax ≥1.5, then these subjects will be defined as having incomplete FES blockade.

Time frame