Treatment of Resistant Metastatic Melanoma Using Decitabine, Temozolomide and Panobinostat

Inclusion Criteria: 1. Male or female patients aged ≥ 18 years old 2. ECOG Performance Status of ≤ 2 3. Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed 4. Patients must have measurable disease according to RECIST and CHOI criteria. The minimum target-lesion diameter should have double the CT slice thickness, i.e., 10 mm 5. Patients must meet the following laboratory criteria: Hematology: Neutrophil count of \>1500/mm3;Platelet count of \> 100,000/mm3L; Hemoglobin ≥ 9 g/dL Biochemistry:AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x upper limit of normal if the transaminase elevation is due to disease involvement;Serum bilirubin ≤ 1.5 x upper limit of normal;Serum creatinine ≤ 1.5 x upper limit of normal or 24-hour creatinine clearance ≥ 50 ml/min; Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal; Serum potassium ≥ lower limit of normal; Serum sodium ≥ lower limit of normal;Serum albumin ≥ lower limit of normal or 3g/dl;Patients with any elevated alkaline phosphatase due to bone metastasis can be enrolled 6. Baseline ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal. 7. TSH and free T4 within normal limits (patients may be on thyroid hormone replacement) 8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 8 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 9. Any patient with the diagnosis of metastatic melanoma from any site. These include untreated patients or those treated with chemotherapy or biochemotherapy. 10. Must not have taken a hypomethylating agent or a histone deacetylase agent in the treatment of their disease. Patients who receive targeted agents would only need a 2-week washout period. 11. Any patient with metastatic melanoma regardless of prior treatment will be eligible. 12. Patients must have had disease progression on or following their most recent treatment regimen or on presentation for the first time with metastatic disease, surgical option can be entertained if this is a localized relapse. 13. Patients with CNS disease are eligible for treatment only after their CNS disease has been directly addressed with radiation therapy. Exclusion Criteria: 1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer 2. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment 3. Impaired cardiac function including any one of the following: Screening ECG with a QTc \> 450 msec confirmed by central laboratory prior to enrollment to the study; 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; Patients with a 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) 4. Uncontrolled hypertension 5. Concomitant use of drugs with a risk of causing torsades de pointes 6. Concomitant use of CYP3A4 inhibitors 7. Patients with unresolved diarrhea \> CTCAE grade 1 8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat 9. Other concurrent severe and/or uncontrolled medical conditions 10. Patients who have received 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. 11. Concomitant use of any anti-cancer therapy or radiation therapy. 12. Patients who have no measurable disease. 13. 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. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months(i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 8 days of the first administration of oral panobinostat. 14. 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 15. Patients with a 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 16. Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required 17. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent