LBH589 in Combination With Capecitabine Plus/Minus (±) Lapatinib in Breast Cancer Patients

Exclusion Criteria

• •1. Prior treatment with an HDAC inhibitor or current treatment with valproic acid.
• •2. Previous treatment with capecitabine.
• •3. Impaired cardiac function including any of the following:
• •* Screening ECG with a QTc \> 450 msec.
• •* Congenital long QT syndrome.
• •* History of sustained ventricular tachycardia.
• •* Any history of ventricular fibrillation or torsades de pointes.
• •* Bradycardia defined as heart rate \< 50 beats per minute. Patients with a pacemaker and heart rate \> 50 beats per minute are eligible.
• •* Myocardial infarction or unstable angina within 6 months of study entry.
• •* Congestive heart failure (NY Heart Association class III or IV).
• •* Right bundle branch block and left anterior hemiblock (bifascicular block).
• •* Atrial fibrillation or flutter.
• •* Ongoing therapy with antiarrhythmics or other medications associated with QTc prolongation.
• •4. Uncorrected hypokalemia or hypomagnesaemia.
• •5. Uncontrolled hypertension (systolic blood pressure \[BP\] 180 or diastolic BP \> 100 mm Hg) or uncontrolled cardiac arrhythmias.
• •6. Active CNS disease, including meningeal metastases.
• •7. Known diagnosis of human immunodeficiency virus (HIV) infection.
• •8. Unresolved diarrhea \> CTCAE grade 1.
• •9. Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors.
• •10. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib.
• •11. Patients with known hypersensitivity to 5-fluorouracil chemotherapy, investigational drug therapy, major surgery \< 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
• •12. Patient is \< 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• •13. Concomitant use of any anti-cancer therapy or radiation therapy.
• •14. Pregnant or breast feeding or female of reproductive potential not using two effective methods of birth control.
• •15. Male patients whose sexual partners are women of childbearing potential not using effective birth control.
• •16. Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
• •17. Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• •18. Patients taking any medications listed in "Prohibited Medications" for both capecitabine and lapatinib .
• •19. Patients with uncontrolled coagulopathy (PT and/or PTT \> 1.2 x ULN; patient must also be on stable dose of anticoagulant for a defined medical indication).
• •20. Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.
• •1\. Prior treatment with lapatinib