Inclusion Criteria:
- 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-only disease with at least one lesion measuring 10 mm or greater in size.
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 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 (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
Exclusion Criteria:
- Participants 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).
- 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.
- 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.