Alpelisib/iNOS Inhibitor/Nab-paclitaxel in Patients With HER2 Negative Metaplastic Breast Cancer (MpBC)

Exclusion Criteria

• •1. Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4. The patient must have discontinued strong CYP3A4 inhibitors or strong CYP3A4 inducers for at least 1 week prior to study treatment initiation (Examples included in Appendix 2).
• •2. Currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis, or otherwise. Therapy with DOACs, heparin, low molecular weight heparin, direct oral anticoagulants or fondaparinux is allowed.
• •3. Concurrent use of medications that interact with nitrate/nitrite levels (Examples included in Appendix 3).
• •4. Received previous treatment with nab-paclitaxel, Pl3K inhibitor, AKT inhibitor, or mTOR inhibitor.
• •5. Known history of Steven Johnson's syndrome or toxic epidermal necrolysis.
• •6. Since HAART agents are metabolized by CYP3A4, HIV positive patients will be excluded from this trial.
• •7. Poorly controlled hypertension at baseline (defined as systolic blood pressure \>150 mm Hg). Isolated, unconfirmed systolic BP elevations will NOT exclude participation. Patients with medication-controlled hypertension are allowed provided they have been on their current medications for at least 4 weeks prior to Cycle 1, Day 1.
• •8. Has any of the following cardiac abnormalities:
• •* Symptomatic congestive heart failure
• •* History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• •* Documented cardiomyopathy
• •* Left ventricular ejection fraction \<50% as determined by multigated acquisition scan or echocardiogram
• •* Myocardial infarction \~6 months prior to enrollment
• •* Unstable angina pectoris
• •* Serious uncontrolled cardiac arrhythmia
• •* Symptomatic pericarditis
• •* History of congenital QT prolongation
• •* Absolute corrected QT interval of \>480 msec in the presence of potassium \>4.0 mEq/L and magnesium \>1.8 mg/dl.
• •9. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks prior to study treatment administration. NOTE: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 3 weeks after the last dose of the previous investigational agent.
• •10. Known or suspected hypersensitivity to any component or excipient of the proposed regimen (nab-paclitaxel, alpelisib, iNOS inhibitor, aspirin).
• •11. Known additional malignancy that requires active treatment.
• •12. Pneumonitis/ interstitial lung disease on baseline CT scan of the chest or moderate to severe chronic lung disease
• •13. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• •14. Manifestations of malabsorption due to prior gastrointestinal surgery, gastrointestinal surgery disease, or an unknown reason.
• •15. Symptomatic/untreated metastatic central nervous system disease.
• •16. Type I diabetes mellitus irrespective of Hgb A1c OR uncontrolled type II diabetes mellitus defined as hemoglobin A1c \>7%.
• •17. Uncontrolled gastric ulcer
• •18. ≥ Grade 2 sensory neuropathy
• •19. Osteonecrosis of jaw
• •20. Pancreatitis
• •21. Pregnant, breastfeeding or expecting to conceive children within the projected duration of the study, starting with the prescreening or screening visit through 30 days after the last dose of study treatment.