Neoadjuvant Chemotherapy Followed by Radiation Therapy and Gemcitabine/Sorafenib/Vorinostat in Pancreatic Cancer

Exclusion Criteria

• •Prior radiotherapy for pancreatic cancer
• •Prior surgical resection of pancreatic cancer
• •Evidence of metastatic disease
• •Any investigational agent within 4 weeks of study treatment initiation
• •Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, any in situ malignancy, or low-risk prostate cancer after curative therapy
• •Intolerance of protocol agents as follows:
• •* Known or presumed intolerance of gemcitabine, vorinostat or sorafenib
• •* Experienced any of the following toxicities with prior gemcitabine adminstration (if given): capillary leak syndrome, posterior reversible encephalopathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, unexplained dyspnea or other evidence of severe pulmonary toxicity, or severe hepatic toxicity
• •Unable to swallow medication
• •Suspected malabsorption or obstruction; note: use of pancreatic enzyme supplements is allowed to control malabsorption
• •Contraindication to antiangiogenic agents, including:
• •* Bronchopulmonary hemorrhage/bleeding event \>= grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] v4.0) within 12 weeks prior to of treatment
• •* Any other hemorrhage/bleeding event \>= grade 3 (CTCAE v4.0) within 12 weeks prior to initiation of treatment
• •* Serious non-healing wound, ulcer, or bone fracture
• •Arterial thrombotic or embolic events such as a myocardial infarction or cerebrovascular accident (including transient ischemic attacks) within the 6 months prior to initiation of treatment. Incidental clinically insignificant embolic phenomena that do not require anti-coagulants are not excluded. Also,tumor-associated thrombus of locally-involved vessels does not count as an exclusion criterion.
• •Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy, recent (within 6 months) myocardial infarction or unstable coronary artery disease
• •Concomitant use of other histone deacetylase (HDAC) inhibitors
• •Planned ongoing administration of STRONG cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers. Examples of clinical inducers and classifications of strong, moderate, and weak interactions are available through the FDA website (Table 3-3 of website): http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm
• •Persistent heart rate (HR) \< 50 or \> 120 beats per minute (bpm).
• •QT(c) ≥ 481 ms (\>= grade 2) on electrocardiogram (ECG) prior to initiation of treatment
• •* Check potassium and magnesium serum levels
• •* Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc
• •* For patients with HR \>60 of \>100 beats per minute (bpm), no manual read of QTc is required
• •* For patients with baseline HR \< 60 or \> 100 bpm, manual read of QT by cardiologist is required, with Fridericia correction applied to determine QTc
• •Planned ongoing treatment with other drugs thought to potentially adversely interact with study drugs; if such medications have been used, patients must be off of these agents for \>= 2 weeks prior to initiation of treatment:
• •* Anticoagulants at therapeutic doses
• •* Immunosuppressants such as tacrolimus, leflunomide or tofacitinib, roflumilast, pimecrolimus
• •Serious uncontrolled infection \> grade 2 (CTCAE v4.0)
• •Medical, psychological, or social conditions that, in the opinion of the investigator, may increase the patient's risk or interfere with the patient's participation in the study or hinder evaluation of the study results