A Single Arm Phase II Trial of Circulating Tumor DNA-guided Adjuvant Therapy With Elacestrant in Adults With Hormone Receptor Positive HER2 Negative Breast Cancers at Risk for Late Recurrence (CATE)
This is a single-arm, phase II study examining elacestrant in the adjuvant treatment of patients with ER+ breast cancer who test positive for circulating tumor DNA (ctDNA) during the screening period of the trial. Our trial will proceed in three separate phases: screening, treatment, and follow-up.
• Women or men aged 18 years and older.
• Previous diagnosis of anatomic stage IIB or anatomic stage III histopathologically or cytologically confirmed ER+, HER2-, breast cancer per local laboratory as per ASCO/CAP guidelines. In the context of this trial, ER status will be considered positive if \>10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without progesterone receptor positivity. Patients with PR positive but ER-negative are not eligible.
• Participants must have been diagnosed with ER+HER2- breast cancer at least five years ago and no more than 20 years ago and must have completed adjuvant endocrine therapy.
• Participants must be off endocrine therapy for at least four weeks prior to screening.
• ctDNA positivity by NEXT Personal assay.
• No evidence of metastatic disease on staging scans.
• a. If imaging, after review with a radiologist, is low probability for metastatic disease, patients may proceed with enrollment. Patients with suspicious but inconclusive imaging results should undergo a diagnostic biopsy; if biopsy is negative patients are eligible for enrollment. Patients with positive imaging that is conclusive of metastatic disease, or biopsy proven metastatic disease, are not eligible.
• At the time of informed consent signature for treatment, participants may be either postmenopausal, premenopausal, or perimenopausal.
• a. Postmenopausal status is defined by: i. Age ≥60. ii. Age \<60 and amenorrhea for 12 or more months (without an alternative cause) and FSH and estradiol level within postmenopausal range per local laboratory reference.
• iii. Documentation of bilateral oophorectomy, at least one month before first dose of trial therapy.
• b. Premenopausal and perimenopausal participants must be willing to concurrently receive an LHRH agonist, and the LHRH agonist must be initiated at least three to four weeks before the start of elacestrant and are planning to continue LHRH agonist treatment during treatment with elacestrant. This is based on the current FDA approval of elacestrant in the metastatic setting which is limited to postmenopausal participants.
• c. Premenopausal or perimenopausal participants must be willing to use a highly effective method of contraception for the duration of trial treatment and for 120 days after the last dose of elacestrant OR if using barrier method of contraception must be willing to use a second form of contraception like occlusive cap with spermicidal foam / gel / film / cream / suppository.
• i. Highly effective methods of contraception are non-hormonal (cooper) intrauterine device (IUD), surgical sterilization (bilateral tubal occlusion/ligation, partner who has had a vasectomy), and sexual abstinence.
• ECOG performance status of 0 or 1.
• Patient has adequate bone marrow and organ function, as defined by the following laboratory values:
‣ Absolute neutrophil count (ANC) \>1.0 x 109/L.
⁃ Platelets \>100 x 109/L.
⁃ Hemoglobin \> 8.0 g/dL.
⁃ Potassium, sodium, calcium, and magnesium CTCAE v5.0 grade \<1.
⁃ Cockcroft-Gault based creatinine clearance \>50 mL/min.
⁃ ALT and AST \<3 x ULN and total serum bilirubin \<1.5 x ULN.
⁃ Hypercholesterolemia and hypertriglyceridemia CTCAE v5.0 grade \<1.