This is non-randomized phase 2 study to evaluate toxicity and efficacy of valproic acid (VA) with concurrent chemoradiotherapy (CCRT) containing weekly gemcitabine in patients with unresectable locally advanced pancreatic cancer (ULAPC). All patients will be planned for three-dimensional conformal radiotherapy (3-DCRT). A total dose of 54 Gy will be delivered using 2 Gy daily fractions given over 5 days a week.Intravenous (i.v.) chemotherapy (ChT) with gemcitabine 300 mg/m2 will be started at the first day of 3-DCRT.Total 5-6 weekly doses of i.v. ChT will be planned.VA will be administered orally in daily dose of 800 mg. Treatment with VA will be commenced at the first day and will be terminated at last day of RT.The patients will be followed till disease progression or death.

Inclusion Criteria:

1. Age > 18 years.

2. Newly-diagnosed, histologically/cytologically or CA 19.9 confirmed ULAPC

3. KPS > 60

4. No previous RT to abdomen

5. No serious comorbid condition Version 1, December 1, 2010

6. No treatment with biological response modifiers or cytotoxic agents within four weeks prior to study entry, apart from induction chemotherapy with gemcitabine

7. No participation in clinical trial using any investigational drug or device within four weeks prior to study entry

8. No serious complication of malignant condition

9. No previous or concurrent malignancy at other sites except cone biopsied in situ carcinoma of the uterine cervix and adequately treated basal cell or squamous cell carcinoma of the skin

10. Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

    • Hemoglobin > 9.0 Gm/dL
    • WBC count > 4.0x109/L
    • Neutrophile count > 1.5 cells x 109/L,
    • Platelet count > 100 x 109/L,
    • Creatinine < 1.5 mg/dL
    • Total bilirubin < upper limit of normal (ULN)
    • AST/SGOT < ULN
    • Calcium < ULN

11. Ability to sign informed consent

12. Ability to attend follow-up visits

Exclusion Criteria:

1. Operable disease

2. Distant metastases

3. KPS < 60

4. Previous RT to abdomen

5. Treatment with biological response modifiers or cytotoxic agents other then induction gemcitabine within four weeks prior to study entry

6. Participation in clinical trial using any investigational drug or device within four weeks prior to study entry

7. Major surgical procedure within two weeks prior to study entry

8. Serious comorbid condition, inclusive but not limited to myocardial infarction within previous six months, uncontrolled cardiac arrhythmias, uncontrolled angina pectoris, active infection including acute hepatitis

9. Serious complication of malignant condition

10. Previous or concurrent malignancy

11. Inadequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

    • Hemoglobin < 9.0 Gm/dL
    • WBC count < 4.0x109/L
    • Neutrophile count < 1.5 cells x 109/L,
    • Platelet count < 100 x 109/L,
    • Creatinine > 1.5 mg/dL
    • Total bilirubin > ULN (upper limit of normal)
    • AST/SGOT > ULN
    • Calcium > ULN

12. Inability to sign informed consent

13. Psychological, familial, sociological or geographical conditions which do permit regular medical follow-up and compliance with the protocol.