Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy

Inclusion Criteria:

* Histological diagnosis of locally advanced or metastatic pancreatic cancer (except neuroendocrine tumors, but including ampullary cancer) with progression after standard first line therapy that included gemcitabine (single agent or combination)
* Measurable disease on computated tomography (CT) scan per Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* At least 28 days from previous systemic therapy, including investigational agents and 1st dose of study treatment and recovered from any acute toxic effects of that treatment before study enrollment.
* Has Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 - Ability to provide written consent
* Must meet hematology and biochemistry laboratory criteria within 14 days of study enrollment:

  * Neutrophil count \>1500/mm\^3
  * Platelet count \>100,000/mm\^L
  * Hemoglobin \> or = 9 g/dL
  * Aspartate aminotransferase (AST/SGOT) or Alanine transaminase (ALT/SGPT) \< or = 2.5 times upper limit of normal (ULN)or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
  * Serum bilirubin \< or = 1.5 x ULN
  * Serum creatinine \< or = 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
  * Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN)
  * Serum phosphorus \> or = LLN
  * Serum potassium \> or = LLN
  * Serum sodium ≥ LLN
  * Serum magnesium ≥ LLN
  * Serum albumin ≥ LLN or 3g/dl
  * Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
* Baseline multi gated acquisition scan (MUGA) or echocardiogram (ECHO) must demonstration left ventricular ejection fraction (LVEF) \> or = 50%
* Normal thyroid function within normal limits. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
* Women of childbearing potential (WOCBP) must have a negative pregnancy tests within 7 days of study treatment administration and willing to use 2 methods of contraception

Exclusion Criteria:

* \> 1 prior systemic treatment regimen for pancreatic cancer
* Prior histone deacetylase (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for treatment of cancer
* Anyone needing valproic acid for any medical condition during the study or 5 days prior to panobinostat treatment
* Impaired cardiac function

  * Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (\<50 beats per minute), QTcF \> 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
  * Presence of atrial fibrillation (ventricular heart rate \>100 bpm)
  * Previous history angina pectoris or acute myocardial infarction (MI) within 6 months of study enrollment
  * Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/Echo shows LVEF \< 50%
* Uncontrolled hypertension defined as hypertensive blood pressure of SBP \> 140 or DBP \> 90, despite antihypertensive medications
* History of deep vein thrombosis (DVT), pulmonary emboli or other blood clotting abnormality within 3 months of study enrollment
* Ongoing need for anti-coagulation therapy except daily low dose aspirin (≤ 100 mg/day) or low molecular weight heparin
* Concomitant use of drugs with risk of causing torsades de pointes
* Anyone with unresolved diarrhea \> or = grade 2 at time of enrollment
* Impairment of gastrointestinal function or disease that may significantly alter the absorption of panobinostat
* Grade 2 or greater peripheral neuropathy within 14 days of enrollment
* Serious concomitant medical or psychiatric disorders (e.g., active infection, uncontrolled diabetes)
* Patients who have received chemotherapy, any investigational agent or undergone major surgery \< 4 weeks prior to starting study drug
* Male patients whose sexual partners are WOCBP and not using double method of contraception during the study and 3 months following.
* Known positivity for human immunodeficiency virus (HIV) or hepatitis C
* Hypersensitivity to bortezomib, boron or mannitol 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