Study of LBH589 (Panobinostat) to Treat Malignant Brain Tumors

Inclusion Criteria:

* Recurrent malignant glioma with radiographic progression
* No more than three prior therapies.
* Male or female patients \>=18 years old
* KPS \>=60.
* Ability to provide written informed consent or consent obtained from responsible healthcare proxy.
* Contrast-enhanced MRI within 2 weeks of enrollment.
* Life expectancy \>= 8 weeks
* Neutrophils \>1500/mm3
* Platelets \> 100,000/mm3L
* Hemoglobin \>=9 g/dL
* AST/SGOT and ALT/SGPT \<= 2.5 x upper limit of normal (ULN) or \< 5.0 x ULN if the transaminase elevation is due to disease involvement
* Serum bilirubin \<= 1.5 x ULN
* Serum creatinine \<= 1.5 x ULN or 24-hour creatinine clearance \>= 50 ml/min
* Total serum calcium or ionized calcium WNL
* Serum potassium WNL
* Serum sodium WNL
* Serum albumin \>= LLN or 3g/dl
* Elevated Alkaline Phosphatase due to bone metastasis can be enrolled
* Baseline MUGA or ECHO must demonstrate LVEF \>= the LLN
* TSH and free T4 WNL (patients may be on thyroid hormone replacement)
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment and must be willing to use two methods of contraception one of them being a barrier method during the study and for 3 months after last study drug administration.
* No concurrent antitumor therapy.
* No enzyme-inducing antiepileptic drugs.
* No significant comorbidities
* Patients must have recovered from toxic effects of prior therapy.

Exclusion criteria

* Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
* Valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
* Impaired cardiac function including:
* Screening ECG with a QTc \> 450 msec
* Congenital long QT syndrome
* History of sustained ventricular tachycardia
* History of ventricular fibrillation or torsades de pointes
* Bradycardia \< 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
* Congestive heart failure (NYHA class III or IV)
* RBBB and LAH (bifascicular block)
* Uncontrolled hypertension
* Concomitant use of drugs with a risk of causing torsades de pointes Concomitant use of CYP3A4 inhibitors
* Patients with unresolved diarrhea
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of LBH589
* Concurrent severe and/or uncontrolled medical conditions
* Chemotherapy, any investigational drug or major surgery \< 4 weeks prior to starting study drug or have not recovered from side effects of such therapy.
* Concomitant use of any anti-cancer therapy or radiation therapy.
* Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method.
* Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom
* 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
* Known human immunodeficiency virus (HIV) or hepatitis C positivity
* Significant history of non-compliance to medical regimens or inability to grant a reliable informed consent
* More than three prior therapies
* Hepatic or renal diseases or any diseases that will obscure toxicity or alter drug metabolism
* Known active malignancies
* Active infection requiring iv antibiotics
* Systemic anticoagulants
* Enzyme-inducing antiepileptic drugs