The goal of this clinical trial is to learn if alisertib in addition to usual care works to treat HR+/HER2+ breast cancer. The main questions it aims to answer are: * Does alisertib stop the communication between HR and HER2? * Are there genetic markers that predict how well someone's cancer will respond to alisertib? Participants will receive alisertib in addition to their usual care.
This pilot clinical trial will evaluate alisertib in combination with standard of care endocrine therapy and Human Epidermal Growth Factor Receptor-2 (HER2)-targeted therapy in participants with Stage IV hormone receptor positive (HR+)/ HER2 positive (HER2+) breast cancer, utilizing our novel 3-gene biomarker signature for patient selection and response prediction
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Alisertib 40mg on days 1-7 of 21-day cycles for 4 cycles
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Clinical benefit defined as partial tumor response (PR)
As defined by RECIST 1.1. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: 12 weeks
Clinical benefit defined as complete tumor response (CR)
As defined by RECIST 1.1 Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
Time frame: 12 weeks
Clinical benefit defined as decline in circulating tumor DNA (ctDNA)
Clinical benefit is defined as a decline in ctDNA by \>50%.
Time frame: 12 weeks
Evaluate safety of adding alisertib to usual care by assessing adverse events
To assess safety, adverse events related to alisertib will be assessed. They will be assessed using CTCAE v6.0.
Time frame: 12 weeks
BRD8 signature expression
The 3-gene BRD8 signature (BRD8/AFF3/RBM24) will be evaluated as a predictive biomarker for response to alisertib combination therapy.
Time frame: 12 weeks
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