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.
The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases. Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. Safety will be monitored initially by a 3+3 design. This will be followed by a phase 2 study to evaluate intracranial progression free survival (PFS). If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Patients will receive single session SRS to intact brain metastases and post-operative cavities. For intact brain metastases, this will be 15 Gy to lesions between 31-40 mm, 18 Gy to 21- 30 mm, and 24 Gy to lesions measuring ≤ 20 mm.
Abemaciclib is an orally administered selective small-molecule inhibitor of CDK4 and CDK6 that is 14 times more potent against CDK4 than CDK6 in enzymatic assays that is approved for the treatment of advanced or metastatic breast cancers. Abemaciclib will be administered at a dose of 150 mg twice daily.
Abemaciclib will be administered with standard of care endocrine therapy. Endocrine therapy can consist of fulvestrant or an aromatase inhibitor. Dosing of concurrent endocrine therapy with abemaciclib should follow standard dosing and safety guidelines.
Moffitt Cancer Center
Tampa, Florida, United States
ACTIVE_NOT_RECRUITINGOhio State University Comprehensive Cancer Center
Columbus, Ohio, United States
RECRUITINGIntracranial Progression Free Survival (PFS)
Intracranial Progression Free Survival: defined as the time from the date of start of treatment to investigator-determined date of progression or death due to any cause, whichever comes first. Progression will be determined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria.
Time frame: Up to 12 months
Intracranial local brain tumor control
Intracranial local brain tumor control following SRS and abemaciclib will be determined from irradiated lesions according to RANO-BM criteria.
Time frame: Up to 12 months
Intracranial distant brain tumor control
Intracranial distant brain tumor control following SRS and abemaciclib will determined by the development of new lesions outside of the irradiated area.
Time frame: Up to 12 months
Extracranial Progression Free Survival
Extracranial Progression Free Survival: Time from the date of start of treatment to the investigator determined date of progression (determined by RECIST) or death due to any cause, whichever occurs first.
Time frame: Up to 12 months
Overall Survival
Overall Survival is defined as the time from the start of treatment to death due to any cause.
Time frame: Up to 12 months
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