STAR Cape+BKM120 MBC With Brain Met

Inclusion Criteria

• Age ≥ 18 years
• Female
• Histologically and/or cytologically confirmed diagnosis of inoperable metastatic breast cancer
• ER+/HER2- OR HER2+ OR triple-negative breast cancer, assessed as ER-, PgR-, and HER2-negative by local laboratory testing; HER2 negative status (based on most recently analyzed biopsy) is defined as IHC status of 0, 1+ or 2+ (if IHC 2+, a negative FISH test is required, ie, HER2 FISH ratio 9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium ≥ the lower limit of normal
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present)
• Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with known Gilbert Syndrome)
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
• Serum amylase ≤ ULN
• Serum lipase ≤ ULN
• Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
• Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
• INR ≤ 2
• Life expectancy > 12 weeks
• Available tissue (blocks and/or slides) samples unless discussed in advance with study principal investigator
• Patient is able to swallow and retain oral medication
• Signed most recent patient informed consent form
• Signed Patient Authorization Form

Exclusion Criteria

• Patient received prior treatment with a P13K inhibitor.
• Patient with known hypersensitivity to BKM120, capecitabine, or their excipients.
• Patient has evidence of impending herniation on baseline brain imaging.
• Patient has evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF.
• Patient has acute or chronic liver, renal disease or pancreatitis (liver metastases are allowed)
• Patients has a mood disorder as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire (PHQ-9 and/or GAD-7):
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• ≥ CTCAE grade 3 anxiety
• Meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
• Patients has diarrhea ≥ CTCAE grade 2
• Patients with uncontrolled hypertension defined as systolic blood pressure 170 or greater or diastolic blood pressure over 100.
• Patient has active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) 480 msec on screening ECG (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
• Conduction abnormality requiring a pacemaker
• Valvular disease with document compromise in cardiac function
• Symptomatic pericarditis
• Patient has a history of cardiac dysfunction including any of the following:
• Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regiona