Panobinostat & Bortezomib in Pancreatic Cancer Progressing on Gemcitabine Therapy

This is an interventional treatment trial for Pancreatic Cancer focused on measuring insulinoma, cancer of pancreas, neoplasms, pancreas, alpha-cell tumor, glucagonoma, beta-cell tumor, somatostatinoma Read More

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