Safety and Efficacy of BKM120 and Lapatinib in HER2+/PI3K-activated, Trastuzumab-resistant Advanced Breast Cancer

Exclusion Criteria

• •1. Previous treatment with lapatinib, neratinib or a PI3K inhibitor
• •2. untreated brain metastases.
• •3. acute or chronic liver, renal disease or pancreatitis
• •4. any peripheral neuropathy ≥ CTCAE grade 2
• •5. any of the following mood disorders, or meets the cut-off score of ≥ 10 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 ideation in the PHQ-9 (independent of the total score of the PHQ-9)
• •* 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)
• •* ≥ CTCAE grade 3 anxiety
• •6. diarrhea ≥ CTCAE grade 2
• •7. active cardiac disease
• •8. history of cardiac dysfunction
• •9. poorly controlled diabetes mellitus (HbA1c \> 8 %)
• •10. Other severe and/or uncontrolled concomitant medical conditions
• •11. Impairment of gastrointestinal function that may significantly alter the absorption of BKM120
• •12. been treated with any hematopoietic colony-stimulating growth factors ≤ 2 weeks prior to starting study drug.
• •13. currently receiving treatment with medication with a known risk prolong the QT interval or inducing Torsades de Pointes
• •14. currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A
• •15. receiving chronic treatment with steroids or another immunosuppressive agent.
• •16. have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies \[other than trastuzumab\] or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
• •17. have received small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy
• •18. have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• •19. have undergone major surgery ≤ 28 days prior to starting study drug or who have not recovered from side effects of such therapy
• •20. Known diagnosis of HIV infection
• •21. History of another malignancy within 3 years
• •22. Patient is unable or unwilling to abide by the study protocol
• •23. pregnant or breast feeding women