The purpose of this study is to evaluate the safety and tolerability of selected dose 1.2mg/kg BID dosage administered subcutaneously (SC) administered PCI-27483 to metastatic or locally advanced pancreatic cancer patients receiving concurrent therapy with intravenously administered gemcitabine for 12 weeks.

This study will be conducted in three segments: Part A, Part B and Part C. Parts A and B are 12 weeks of treatment followed by 4 weeks of evaluation. In part A patients will dose-escalate up to three dose levels of PCI-27483 administered as subcutaneous (SC) injections twice-daily (BID). Part B to start once 4th patient completes 90 of 112 doses in 8 weeks. In part B patients are randomized to PCI-27483 and gemcitabine (active arm) OR gemcitabine only (control arm). PCI-27483 doses in both Part A and B will be administered in combination with a standard regimen of gemcitabine. Patients with a tumor response or stable disease at 12 weeks will have the opportunity to continue PCI-27483 treatment until disease progression or the Investigator considers the study treatment to be no longer tolerable. Treatment with gemcitabine in either the active or control arm may continue until a standard course of gemcitabine therapy has been completed. Patients will complete Part A or Part B after 16 weeks on study regardless of treatment duration. Evaluable patients will roll over into part C and be followed for 12 months from enrollment (first dose).

Inclusion Criteria:

1. Men or women at least 18 years old

2. Body weight ≥ 40 and ≤ 100 kg.

3. Part A: Metastatic ductal adenocarcinoma of the pancreas diagnosed ≤ 4 months prior to enrollment. (Locally advanced does not have any criteria)

4. Part B: Locally advanced ductal adenocarcinoma of the pancreas diagnosed ≤ 3 months prior to enrollment or metastatic ductal adenocarcinoma diagnosed ≤ 2 months.

5. Measurable disease by spiral CT scan (SCT) in accordance with RECIST criteria.

6. Patients after non-curative surgery are eligible if at least 4 weeks after surgery and recovered from significant surgical morbidity.

7. Estimated life expectancy of at least 4 months.

8. ECOG performance status 0 to 1.

9. Normal baseline coagulation function as defined by:

   1. PT 10-16 seconds, and
   2. aPTT 22-38 seconds.

10. Agree to not participate in contact sports or strenuous activity while taking PCI-27483.

11. Ability to understand the study, willingness to participate in the study for the study duration, and ability to provide written informed consent to participate.

Exclusion Criteria:

1. History of any clinically significant medical condition that, in the opinion of the Principal Investigator, would interfere with the study evaluation or interpretation.

2. Known history of brain metastases.

3. Any evidence of intra-cranial hemorrhage based on head CT scan within 30 days of enrollment.

4. History of disease progression while being treated with gemcitabine.

5. Radiotherapy of the primary tumor or unwillingness to defer radiotherapy of the primary tumor until > 3 months from initiation of treatment.

6. History of venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism,and arterial thromboembolism) or other indications for anticoagulant treatment (eg,mechanical heart values, atrial fibrillation, etc.) within the last year. Local thrombus in the mesenteric or portal vein is acceptable.

7. Uncontrolled hypertension (systolic > 160 or diastolic > 100 mm Hg on medical treatment).

8. Continued anticoagulation therapy or anticoagulation therapy within 2 months prior to enrollment, except for perisurgical prophylaxis which must have ceased 2 weeks before enrollment.

9. Contraindication to systemic anticoagulation.

10. Continued treatment with antiplatelet drugs including aspirin, clopidogrel, etc. within the past 72 hours.

11. Known history of clinically significant or recurrent bleeding episodes, including significant bleeding after surgery, childbirth, or dental extraction.

12. Patients with documented invasion of adjacent organs by CT scan (e.g. stomach, duodenum) are not eligible

13. Patients known to have esophageal varicose are not eligible

14. Known history of a congenital coagulation factor deficiency.

15. Known acquired or hereditary platelet disorder.

16. Known history of immunodeficiency.

17. Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.

18. Pregnant or lactating women (female patients of childbearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or if positive, pregnancy ruled out by ultrasound).

19. Laboratory Abnormalities:

    1. Serum creatinine > 2 mg/dL or creatinine clearance < 50 mL/minute (using Cockroft Gault formula)
    2. AST and ALT ≥ 4.0 x upper limit of normal (ULN).
    3. Bilirubin ≥ 3 mg/dL.
    4. Alkaline phosphatase > 5 x ULN.
    5. Albumin < 2.0g/dL.
    6. Hemoglobin < 9.0 g/dL.
    7. Platelet count < 100,000/μL.

20. Evidence of active gastrointestinal tract bleeding, including guaiac stool positivity,excluding hemorrhoidal bleeding

21. Chronic active hepatitis B or C.

22. Known HIV infection.

23. Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to enrollment, or planned participation within the study duration.

24. Risk factors for, or use of medications known to prolong QTc interval or that may be associate with Torsades de Pointes within 7 days of treatment start (see Appendix J. Risk Factors for Drug-induced Torsades de Pointes).

25. QTc prolongation (defined as a QTc ≥ 450 msec) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If 2 screening ECGs have a QTc ≥ 450 msec, the ECGs can be submitted for a centralized, cardiologic evaluation and if determined to be < 450 msec then the patient is eligible.