Abemaciclib and Elacestrant for the Treatment of Patients with Hormone Receptor Positive/HER2 Negative Breast Cancer with Brain Metastasis

Inclusion Criteria

• Post-menopausal women with histologically or cytologically diagnosed metastatic HR+/Her2- breast cancer defined as positive for estrogen receptor or progesterone receptor (more than 1% staining by immunohistochemistry, as defined in 2010 American Society for Clinical Oncology (ASCO) recommendations, Hammond 2010) and negative for HER2 amplification (immunohistochemistry result of 0-1+, or a negative in situ hybridization). Post-menopausal status is defined as: * Documented surgical bilateral oophorectomy * Age > 59 years with amenorrhea for > 1 year since last menses * Age < 60 years with amenorrhea for > 1 year since last menses and serum estradiol and follicle stimulating hormone (FSH) in post-menopausal laboratory range
• Patients must have measurable brain metastasis (patients with leptomeningeal disease and measurable parenchymal disease are permitted) with documented intracranial disease progression. One measurable lesion > 5mm, or previously irradiated lesion with increase in size by at least 5mm as defined by RANO-BM criteria and revised RECIST criteria (version 1.1) as per assessment by treating medical doctor (MD). Patients with prior whole brain radiotherapy are permitted
• Prior treatment with unlimited lines of systemic chemotherapy for metastatic disease and two weeks from any previous anticancer therapy including biologics and recovered from expected toxicity; at least 4 weeks from major surgery and recovered; at least 3 weeks from radiation affecting more than 25% of bone marrow and recovered; and 2 weeks from other palliative radiation and recovered
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] grade ≤ 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy)
• Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 2 weeks (14 days) is required between end of radiotherapy and randomization
• Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
• Platelets ≥ 100 × 10^9/L
• Hemoglobin ≥ 8 g/dL
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN). Patients with Gilbert’s syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Serum creatinine ≤ 1.5 × ULN
• Ability to swallow oral medications
• Women of child-producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 120 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential
• Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments
• Availability of archival tumor tissue (core biopsy, needle-based biopsy, or surgical tumor blocks) for analysis. Sites will be asked to submit archival tissue (study patients may start the study if tissue is available at an outside hospital, but not yet requested or received). ). If available, both primary breast tumor and metastatic tumor from the patient, will be used. But if the patient can only provide either a primary breast tumor or metastatic tumor, but not both, then this will be allowable, and the patient will still be considered eligible. In addition, if the patient does not have archival tissue, but they can provide the required plasma that is requested as part of the protocol, then the patient can still be eligible

Exclusion Criteria

• Females who are pregnant or lactating and men
• Patients under the age of 18
• Prior use of abemaciclib and elacestrant in combination. (The use of other cdk4/6 inhibitors are allowed, as well as, abemaciclib or elacestrant with at least 6 months from prior exposure to either.)
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
• The patient has active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
• Women who are pre-menopausal (women with chemically induced menopause or receiving ovarian suppression are eligible)
• More than two seizures in the last 4 weeks
• Have uncontrolled serious medical or psychiatric illness
• Have any medical condition that would impair the administration of oral agents including recurrent bowel obstructions, inflammatory bowel disease or uncontrolled nausea, vomiting. Baseline grade 2 or greater diarrhea
• Have an additional malignancy diagnosed within 5 years of study enrollment with the exception of basal or squamous cell skin cancer or cervical cancer in situ
• Patients may not be receiving any other investigational agents. A washout period of 14 days is required for all prior anti-cancer therapies
• Unable or unwilling to avoid prescription medications, over-the-counter medications, dietary/herbal supplements (eg, St. John’s wort), and/or foods (eg, grapefruit, pomelos, star fruit, Seville oranges and their juices) that are moderate/strong inhibitors or inducers of CYP3A4 activity. Participation will be allowed if the medication, supplements, and/or foods are discontinued for at least 5 half-lives or 14 days (whichever is longer) prior to study entry and for the duration of the study