ERα+ Breast CancerEarly Phase 1NCT04174352
FES Imaging to Optimize Tamoxifen for Metastatic Breast Cancer
A Early Phase 1 study testing Tamoxifen and FES PET/CT in people with ERα+ Breast Cancer and ESR1 Gene Mutation, run by University of Wisconsin, Madison at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- ERα+ Breast Cancer, ESR1 Gene Mutation
- What is being tested?
- Tamoxifen and FES PET/CT
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Oct 2020to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologically confirmed breast cancer that is metastatic or unresectable with the following:
- 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.
- Participants must have received at least 1 prior line of endocrine therapy in the metastatic setting or have had progression within 12 months of adjuvant endocrine therapy. Prior Tamoxifen is allowed in any setting. Prior CDK4/6 in the metastatic setting per NCCN guidelines is allowed.
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- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (See Appendix A)
- Life expectancy of greater than 12 weeks.
- Ability to take oral medications.
- Informed consent: participant must be informed of the investigational nature of the study and must be able to sign a written informed consent.
- Participants with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiation, or stereotactic radiosurgery) for at least 1 month.
- Participants must have adequate normal organ and bone marrow function as defined below:
- Absolute neutrophil count >/= 1,000/mcL
- Hemoglobin >/= 9.0 g/dL
- Platelets >/= 100,000/mcL
- Total bilirubin </= 1.5 x upper limit of normal (ULN)
- AST (SGOT)/ ALT (SGPT) </= 2.5 x ULN; </= 5 x ULN in the setting of metastatic liver disease
- Creatinine </= 1.5 x ULN or creatinine clearance >/= 50 mL/min
Who cannot join
- 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.
- Current optic nerve disorders, retinopathy, lattice degeneration, macular degeneration, retinal vascular disorder, or retinal tears of severity greater than grade 1.
- History of cerebellar disorders, ataxia, and uncontrolled seizures unless related to transient medical condition and in investigator's opinion is not an active medical issue.
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- History of venous thrombosis/thromboembolic event, including pulmonary embolism and stroke.
- Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 470msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, chronic hypokalemia, family history of long QT interval syndrome).
- Are taking medications that are known to prolong the QT interval, unless they can be transferred to other medications ≥ 5 half-lives prior to dosing or unless the medications can be properly monitored during the study. If equivalent medication is not available, QTcF should be closely monitored.
- Tamoxifen has demonstrated vaginal bleeding, birth defects and fetal loss in pregnant women. Tamoxifen use during pregnancy may have a potential long-term risk to the fetus of a Diethylstilbestrol syndrome (DES)-like syndrome. Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative urine/serum pregnancy test within 14 days of tamoxifen treatment). In addition, a medically acceptable method of birth control must be used such as an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for 3 months after last dose of study drug. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP.
- Ongoing treatment with other investigational agents. Participants cannot be receiving concomitant chemotherapy, radiotherapy, experimental therapy or any other therapy not otherwise outlined by the trial for the purposes of anti-cancer treatment.
- History of uterine malignancy unless participant has had hysterectomy with no evidence recurrent disease for ≥ 3 years from definitive therapy.
- Concurrent malignancy except for the following:
- Basal cell or squamous cell skin cancer
- In situ cervical cancer
- The following medications are contraindicated or must be used with caution.
- Contraindicated:
- CYP2D6, CYP3A4, and CYP2C9 strong inhibitors
- CYP2D6, CYP3A4, and CYP2C9 strong inducers
- Use with caution:
- CYP2C9 sensitive substrates
- CYP2D6 moderate inhibitors or inducers
- CYP3A4 moderate inhibitors or inducers
- Note: Transdermal products designed for systemic delivery must be assessed for interaction potential. Topical products not designed to provide systemic delivery (including inhaled products, ophthalmologic products and transvaginal preparations) do not need to be considered.
- Contraindicated medications are not allowed. Participants taking these concurrent medications are ineligible unless they can discontinue or switch to alternative medications prior to initiation of study drug (at least 5 half-lives).
- Use with caution agents are permitted if a) discontinuation is not feasible or b) no acceptable alternatives are available as determined by the treating physician; however, caution should be used. Consider monitoring by symptoms, labs or drug levels and dose adjustments of the medication.
- Uncontrolled intercurrent clinically significant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Cancer Connect, 800-622-8922, clinicaltrials@cancer.wisc.edu
Kari Wisinski, MD
- Not yet recruiting
Wisconsin Oncology Network (WONIX) sites
Madison, Wisconsin, 53792
Cancer Connect, 800-622-8922, clinicaltrials@cancer.wisc.edu
About this study
Official title: A Pilot Study of FES Imaging to Optimize Tamoxifen Dose for Metastatic Breast Cancer Patients With ESR1 Mutations
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.
- Conditions
- ERα+ Breast Cancer, ESR1 Gene Mutation
- Being tested
- Tamoxifen, FES PET/CT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamoxifenDrug
estrogen modulator
FES PET/CTDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| Tamoxifen Dose Levels | Experimental | Three participants will be enrolled to each dose level of oral tamoxifen (n = 12)
Dose Level 1 = 20 mg daily Dose Level 2 = 80 mg daily Dose Level 3 = 160 mg daily Dose Level 4 = 200 mg daily
Tamoxifen should be started within 14 days of the FES-PET/CT scan, at least 24 hours after FES injection. Participants will continue tamoxifen therapy until there is radiologic or clinical evidence of progressive disease or drug intolerance. Receives: Drug: Tamoxifen; Diagnostic Test: FES PET/CT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 6 weeks to compare baseline and treatment images
Secondary outcomes (6)
FES uptake at each dose level: SUVmax
FES uptake will be quantified on 5 target lesions using standardized uptake value (SUV) measurements including SUVmax, SUVmean, SUVpeak, Tumor-to-Normal (T/N) tissue ratio, and Tumor-to-Blood Pool ratios.
Measured: up to 6 weeks to compare baseline and treatment images
FES uptake at each dose level: SUVmean
FES uptake will be quantified on 5 target lesions using standardized uptake value (SUV) measurements including SUVmax, SUVmean, SUVpeak, Tumor-to-Normal (T/N) tissue ratio, and Tumor-to-Blood Pool ratios.
Measured: up to 6 weeks to compare baseline and treatment images
FES uptake at each dose level: Tumor-to-Normal tissue ratio
FES uptake will be quantified on 5 target lesions using standardized uptake value (SUV) measurements including SUVmax, SUVmean, SUVpeak, Tumor-to-Normal (T/N) tissue ratio, and Tumor-to-Blood Pool ratios.
Measured: up to 6 weeks to compare baseline and treatment images
FES uptake at each dose level: Tumor-to-Blood Pool ratio
FES uptake will be quantified on 5 target lesions using standardized uptake value (SUV) measurements including SUVmax, SUVmean, SUVpeak, Tumor-to-Normal (T/N) tissue ratio, and Tumor-to-Blood Pool ratios.
Measured: up to 6 weeks to compare baseline and treatment images
Objective Response Rate at each dose level
The objective response rate is the proportion of all participants with confirmed Partial Response or Complete Response according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).
Measured: up to 6 months
Safety: Number of Participants Experiencing Grade 3 or higher Adverse Events
All grade 3-4 adverse events occurring between cycle 1, day 1 to cycle 2 day 1 and at least possibly related to therapy will be reviewed by the principal investigator prior to starting enrollment in the next dose cohort. If 2 or more of the 3 participants in any cohort experience grade 3-4 adverse events, then dose escalation will be halted.
Measured: Up to 21 days on treatment (up to 6 weeks on study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start20 Oct 2020
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ERα+ Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- a single-arm, open-label, pilot study of escalating doses of tamoxifen
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kari Wisinski, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04174352
- Sponsor's protocol ID
- 2019-0935
- Other IDs
- UW19046, A534260, SMPH/MEDICINE/MEDICINE, Protocol Ver v.5.0 1/8/2024, AAH4731, NCI-2019-07924
- Status last verified
- Dec 2025
- First submitted
- 21 Nov 2019
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of FES Imaging to Optimize Tamoxifen Dose for Metastatic Breast Cancer Patients With ESR1 Mutations
- ClinicalTrials.gov ID
- NCT04174352
- Acronym / sponsor ID
- 2019-0935
- Conditions
- ERα+ Breast Cancer, ESR1 Gene Mutation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 22 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- a single-arm, open-label, pilot study of escalating doses of tamoxifen
| Arm | Type | Receives |
|---|---|---|
| Tamoxifen Dose Levels | Experimental | Drug: Tamoxifen, Diagnostic Test: FES PET/CTThree participants will be enrolled to each dose level of oral tamoxifen (n = 12) Dose Level 1 = 20 mg daily Dose Level 2 = 80 mg daily Dose Level 3 = 160 mg daily Dose Level 4 = 200 mg daily Tamoxifen should be started within 14 days of the FES-PET/CT scan, at least 24 hours after FES injection. Participants will continue tamoxifen therapy until there is radiologic or clinical evidence of progressive disease or drug intolerance. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Participants must have histologically confirmed breast cancer that is metastatic or unresectable with the following:
- 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.
- Participants must have received at least 1 prior line of endocrine therapy in the metastatic setting or have had progression within 12 months of adjuvant endocrine therapy. Prior Tamoxifen is allowed in any setting. Prior CDK4/6 in the metastatic setting per NCCN guidelines is allowed.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (See Appendix A)
- Life expectancy of greater than 12 weeks.
Key exclusion criteria (27 listed)
- 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.
- Current optic nerve disorders, retinopathy, lattice degeneration, macular degeneration, retinal vascular disorder, or retinal tears of severity greater than grade 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tamoxifenestrogen modulator | Drug | Tamoxifen Dose Levels |
| FES PET/CTRadiolabeled 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. | Diagnostic test | Tamoxifen Dose Levels |
Primary outcome
Rate of FES Blockade at each dose level to determine the Optimal Tamoxifen Dose
Time frame: up to 6 weeks to compare baseline and treatment images
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.
6 secondary outcomes
FES uptake at each dose level: SUVmax
Time frame: up to 6 weeks to compare baseline and treatment images
FES uptake at each dose level: SUVmean
Time frame: up to 6 weeks to compare baseline and treatment images
FES uptake at each dose level: Tumor-to-Normal tissue ratio
Time frame: up to 6 weeks to compare baseline and treatment images
FES uptake at each dose level: Tumor-to-Blood Pool ratio
Time frame: up to 6 weeks to compare baseline and treatment images
Objective Response Rate at each dose level
Time frame: up to 6 months
Safety: Number of Participants Experiencing Grade 3 or higher Adverse Events
Time frame: Up to 21 days on treatment (up to 6 weeks on study)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kari Wisinski, MD principal investigator
University of Wisconsin, Madison
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tamoxifen and FES PET/CT in people with ERα+ Breast Cancer and ESR1 Gene Mutation, run by University of Wisconsin, Madison at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact cancer connect (800-622-8922, clinicaltrials@cancer.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of FES Blockade at each dose level to determine the Optimal Tamoxifen Dose (time frame: up to 6 weeks to compare baseline and treatment images). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.