Clinical trial NCT01056601 (phase 2, status: terminated)
Conditions: pancreatic cancer
ICD codes: C25.3
Drugs: bortezomib, panobinostat
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, [H]\C(=C(\[H])C1=CC=C(CNCCC2=C(C)NC3=CC=CC=C23)C=C1)C(O)=NO
Reason stopped: 
    funding not available
  
Eligibility criteria:

        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