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FES-PET / CT Scans for the Optimization of Tamoxifen Dose in Patients with Estrogen Receptor Positive, ESR1 Mutant Metastatic or Unresectable Breast Cancer

Trial Status: Active

This early phase I trial studies how well FES-PET / CT scans work in determining the best dose of tamoxifen for treating patients with estrogen receptor positive, ESR1 gene mutant breast cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). FES is a low-dose radioactive form of estrogen and can "light up" where estrogen receptor positive cancer is present in the body. Diagnostic procedures such as FES-PET / CT, may help to determine the optimal dose of tamoxifen and prevent treatment resistance due to underdosing on standard dose of tamoxifen in patients with breast cancer.

Inclusion Criteria

  • Patients must have histologically confirmed breast cancer that is metastatic or unresectable with the following: * Estrogen receptor expression by immunohistochemistry >= 10% * ESR1 mutation identified using a Clinical Laboratory Improvement Act (CLIA) certified assay via tumor biopsy tissue or circulating free deoxyribonucleic acid (DNA) (cfDNA) * HER2 negative
  • Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or evaluable bone-only disease with at least one lesion measuring 10 mm or greater in size. Patients with liver-only disease are not eligible due to the inherent hepatic uptake related to the radiopharmaceutical’s hepatobiliary route of elimination
  • Patients must have received at least 1 prior line of non-tamoxifen containing endocrine therapy in the metastatic setting or have had progression within 12 months of adjuvant non-tamoxifen endocrine therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Life expectancy of greater than 12 weeks
  • Ability to take oral medications
  • Informed consent: patients must be informed of the investigational nature of the study and must be able to sign a written informed consent
  • Patients 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
  • 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)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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

Exclusion Criteria

  • Patients must have received at least 1 prior line of non-tamoxifen containing endocrine therapy in the metastatic setting or have had progression either while taking or within 12 months of adjuvant non-tamoxifen endocrine therapy (i.e. on or within 12 months of an aromatase inhibitor)
  • 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)
  • Patients 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
  • History of venous thrombosis/thromboembolic event, including pulmonary embolism and stroke
  • Have a heart-rate corrected QT interval (using Fridericia’s formula) (QTcF) >= 470 msec 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 (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. Patients 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 patient 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. Patients 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


University of Wisconsin Hospital and Clinics
Status: ACTIVE
Contact: Kari Braun Wisinski
Phone: 608-262-2876


I. To determine the optimal dose of tamoxifen for adequate ERalpha inhibition as determined by F-18 16 alpha-fluoroestradiol (FES)-positron emission tomography (PET)/computed tomography (CT) and safety profile in patients with ESR1-mutant breast cancer.


I. To assess the feasibility of evaluating FES uptake changes with escalating tamoxifen doses in ESR1-mutant breast cancer.

II. To observe and record anti-tumor activity of escalating doses of tamoxifen.

III. To observe the safety and tolerability of escalating doses of tamoxifen.


I. To explore resistance mutations in ESR1 via mandated liquid biopsy at time of progression.

OUTLINE: This is a dose-escalation study of tamoxifen.

Patients receive F-18 16 alpha-fluoroestradiol intravenously (IV) and undergo PET/CT scan at baseline. Starting within 14 days of FES-PET/CT scan, patients with at least 1 FES positive lesion receive tamoxifen orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks after initiation of tamoxifen therapy, patients undergo a second FES-PET/CT scan.

After completion of study, patients are followed up periodically.

Trial Phase Phase O

Trial Type Treatment

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Kari Braun Wisinski

  • Primary ID UW19046
  • Secondary IDs NCI-2019-07924, 2019-0935
  • ID NCT04174352