Vorinostat Plus Radiation Therapy in Pancreatic Cancer

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
2. Patients must be \>/= 18 years of age. There will be no upper age restriction.
3. Cytologic or histologic proof of adenocarcinoma of the pancreas. Patients can have tumor originating in any part of the pancreas. Islet cell tumors are not eligible. Only patients with non- metastatic, unresectable disease (American Joint Committee on Cancer (AJCC) 2002 stage T4 NX M0) are eligible. Patients who cannot undergo resection because of underlying medical problems are also eligible. Patients with regional nodal disease are eligible.
4. All patients must be staged with a physical exam, chest x-ray/CXR, and contrast-enhanced helical thin-cut abdominal CT. Unresectability is defined by CT criteria: a) evidence of tumor extension to the celiac axis or superior mesenteric (SM) artery, or b) evidence on either CT or angiogram of occlusion of the SM vein or SM/ portal vein confluence. If a tumor does not meet this definition and is found to be unresectable at surgical exploration, then that tumor is considered unresectable.
5. Patients may have received prior chemotherapy but not prior radiation therapy to the upper abdomen.
6. Bone marrow function: absolute neutrophil count (ANC) \>1,500/ul. Platelets \>100,000/ul.
7. Hepatic function: Total bilirubin less than 1.5mg/dL. If the patient required an endobiliary stent and/or external biliary drain, the bilirubin level must have declined on consecutive measurements indicating adequate biliary decompression; alanine aminotransferase (ALT) \</= 5 times the upper limit of normal.
8. Renal function: Blood urea nitrogen (BUN) \</= 30 mg% and creatinine \</= 1.5 mg%
9. Patients must be willing to sign informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary.

Exclusion Criteria:

1. Prior abdominal radiotherapy.
2. Participation in any other experimental drug study in the 30 days preceding initiation of treatment on the current study.
3. Prior treatment with HDAC inhibitors (except valproic acid with a 30-day washout period)
4. Prior history of cancer within the last five years except for basal cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with previous malignancies but without evidence of disease for 5 years will be allowed to enter the trial.
5. Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Women / men of childbearing potential not using a reliable contraceptive method (oral contraceptive, other hormonal contraceptive, intrauterine device, diaphragm or condom). (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 30 days from the date of the last study drug administration.
6. Serious, uncontrolled, concurrent infection(s) requiring intravenous (IV) antibiotics or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
7. Current treatment of active hepatitis virus or HIV infection with interferon, ribavirin, telbivudine, entecavir, lamivudine, adefovir, efavirenz, zidovudine, tenofovir, emtricitabine, or ritonavir.
8. Psychiatric disorders rendering patients incapable of complying with the requirements of the protocol.
9. Inability to comply with study and/or follow-up procedures.