Phase I/II Study of Stereotactic Radiation and Abemaciclib in the Management of Hormone Receptor Positive HER2 Negative Breast Cancer Brain Metastases
This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.
Phase 1 Primary: Evaluate the safety and feasibility of abemaciclib to sites of brain metastases in the management of HR+/HER2- metastatic breast cancer with brain metastases.
Phase II Primary: Determine PFS intracranially following SRS and abemaciclib in the management of HR+/HER2- metastatic breast cancer with brain metastases.
Secondary: Determine PFS extracranially following SRS and abemaciclib in the management of HR+/HER2- metastatic breast cancer with brain metastases.
Evaluate the intracranial local brain tumor control following SRS and abemaciclib in the management of HR+/HER2- metastatic breast cancer with brain metastases.
Evaluate the intracranial distant brain tumor control following SRS and abemaciclib in the management of HR+/HER2- metastatic breast cancer with brain metastases.
Determine overall survival (OS) following SRS and abemaciclib in the management of HR+/HER2- metastatic breast cancer with brain metastases.
HR+ breast cancer to fulfill the requirement of HR+ disease, a breast cancer must express (≥ 1%), by immunohistochemistry (IHC), at least 1 of the hormone receptors (estrogen receptor [ER] or progesterone receptor [PR]) as defined in the American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) Guidelines
To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined by the ASCO / CAP Guidelines
> Able to swallow oral medications
Willing to comply with all study procedures and available for duration of the study
Measurable brain disease per RANO-BM criteria that can be measured in at least one dimension as > 0.5 cm for both intact brain metastases and post-operative cavities
Eligible for SRS to brain metastases or to the post-operative bed following surgical resection
Maximum diameter of the largest intact brain metastases > Eastern Cooperative Oncology Group performance status 0 to 2
A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies. If attempts to obtain archival tissue are unsuccessful the patient may be enrolled.
Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will be allowed if active measurable disease has not previously been treated with radiation therapy
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 7 days of the first dose of abemaciclib
WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s), and for three weeks following the last dose of abemaciclib
Prior receipt of abemaciclib in the setting of brain metastases or in the past 6 months for the treatment of metastatic disease.
All toxicities attributed to prior anticancer therapy must have been resolved to Grade 1 (NCI CTCAE Version 5) or baseline before administration of study drug(s) other than: a. Toxicities attributed to prior anticancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy b. Toxicities that are not expected to interfere with study treatment, such as fatigue, alopecia, or grade 2 hematologic toxicity
Women who are pregnant or breastfeeding
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 > The patient has active systemic 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
Patients with prior history of nonbreast cancer malignancies should have no evidence of disease > 2 years
Major surgery or significant traumatic injury that has not been recovered from by 14 days before the initiation of study drug
Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of first dose of study treatment
History of allergy or hypersensitivity to any of the study drugs or study drug components
Prisoners or individuals who are involuntarily incarcerated
Please call 1-888-663-3488 for support from a Moffitt representative. New Patients and Healthcare Professionals can submit an online form by selecting the appropriate button below. Existing patients can call 1-888-663-3488. Click here for a current list of insurances accepted at Moffitt.
NEW PATIENTS To request a new patient appointment, please fill out the online form or call 1-888-663-3488.
REFERRING PHYSICIANS Providers and medical staff can refer patients by submitting our online referral form.
Moffit now offers Virtual Visits for patients. If you are eligible for a virtual appointment, our scheduling team will discuss this option further with you.
Moffitt Cancer Center is committed to the health and safety of our patients and their families. For more information on how we’re protecting our new and existing patients, visit our COVID-19 Info Hub