This phase I trial studies the side effects of stereotactic radiosurgery with abemaciclib, ribociclib, or palbociclib in treating patients with hormone receptor positive breast cancer that has spread to the brain (brain metasteses). Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Abemaciclib, ribociclib, and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib, ribociclib, or palbociclib concurrently with stereotactic radiosurgery may reduce the side effects and/or increase the response to each of the therapies.
PRIMARY OBJECTIVE: I. Prospectively evaluate safety and toxicity of the combination of radiosurgery (SRS) and concurrent CDK 4/6 inhibitors (CDKi) for hormone receptor positive (HR+) breast cancer patients. SECONDARY OBJECTIVES: I. Evaluate late toxicity (after 3 months) following SRS and concurrent CDKi. II. Evaluate local control efficacy with combination therapy of SRS and concurrent CDKi. III. Assess quality of life and neurologic functional outcomes following treatment using standardized questionnaire (Functional Assessment of Cancer Therapy-Brain \[FACT-Br\]). IV. Analyze overall survival. OUTLINE: Patients are assigned to 1 of 3 groups. GROUP I: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive abemaciclib orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity. GROUP II: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive ribociclib PO once daily (QD) on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity. GROUP III: Beginning within 2 weeks prior to stereotactic radiosurgery, patients receive palbociclib PO QD on days 1-21. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, 4-6 weeks post stereotactic radiosurgery, and then every 3 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Incidence of grade 3+ radiation therapy oncology central nervous system toxicity
Rate and frequency of grade 3+ toxicity will be reported. A 95% exact confidence interval will be estimated using the Clopper-Pearson method.
Time frame: At 3 months
Symptomatic radiation necrosis (late toxicity)
Will be defined as radiographic (typically on magnetic resonance imaging) changes consistent with radiation induced necrosis and the patient presenting with increased neurological symptoms. Rate and frequency of late toxicity will be reported, and a 95% exact confidence interval will be estimated. Symptomatic radiation necrosis similarly will be summarized. The rate of radiation necrosis will be compared with that of our institutional historical control.
Time frame: At 6 and 12 months
Intracranial failure within treated lesion
Will be defined by progressive lesion either biopsy-proven or with imaging interpretation concordance by both radiation oncologist and neuroradiologist on serial imaging. The cumulative incidence approach will be used to estimate the failure rates for intracranial failure of treated lesion and distant intracranial failures.
Time frame: Up to 1 year
Distant intracranial failure
New lesions will be defined by new contrast-enhancing brain lesions on magnetic resonance imaging. The cumulative incidence approach will be used to estimate the failure rates for intracranial failure of treated lesion and distant intracranial failures.
Time frame: Up to 1 year
Overall survival
The Kaplan-Meier method will be used to estimate the overall survival rates.
Time frame: Up to 1 year
Quality of life (QoL)
Will be assessed by Functional Assessment of Cancer Therapy-Brain (FACT-Br) at pre- and post-radiosurgery. Will be summarized using frequencies and percentages for categorical variables, and mean, standard deviation, median, and range for continuous variables. Paired tests such as paired t-tests and McNemar's tests will be considered for comparing QoL outcomes pre- versus post-radiosurgery.
Time frame: Up to 1 year
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