Panobinostat and Fluorouracil Followed By Leucovorin Calcium in Treating Patients With Stage IV Colorectal Cancer Who Did Not Respond to Previous Fluorouracil-Based Chemotherapy

Exclusion Criteria

• •Male patients whose sexual partners are WOCBP not using effective birth control
• •May not have received any other investigational agents within 28 days of study entry (chemotherapy, any investigational drug or undergone major surgery \< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy).
• •May not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
• •Patients with known brain metastases are excluded from this clinical trial
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to LBH589; including sodium butyrate, trichostatin A (TSA), trapoxin (TPX), MS-27-275 and depsipeptide
• •Severe and/or uncontrolled 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
• •Pregnant or breast feeding or patients of reproductive potential not using two effective methods of birth control; women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
• •History of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
• •Unresolved diarrhea \> CTCAE grade 1
• •Acute infection requiring intravenous antibiotic, antiviral, or antifungal medications within 2 weeks prior to the start of study drugs
• •Known positivity for human immunodeficiency virus (HIV) or hepatitis C
• •Screening ECG with a QTc \> 450 msec
• •Patients with 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)
• •Prior cancer treatment with an HDAC inhibitor (e.g., vorinostat, Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid)
• •Uncontrolled hypertension
• •Concomitant use of drugs with a risk of causing torsades de pointes
• •Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
• •Patients needing valproic acid for any medical condition during the study or within 5 days prior to first LBH589