PEGPH20 Plus Gemcitabine With Radiotherapy in Patients With Localized, Unresectable Pancreatic Cancer

Inclusion Criteria: Subjects must satisfy all the following inclusion criteria to be enrolled in the study: 1. Signed, written Institutional Review Board/Ethics Committee-approved Informed Consent Form; 2. For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study. Effective contraceptive methods consist of prior sterilization, intra-uterine device, oral or injectable contraceptives, and/or barrier methods. Abstinence alone is not considered an adequate contraceptive measure for the purposes of this study; 3. Patients with previously untreated localized, unresectable histologically confirmed pancreatic adenocarcinoma (unresectable will be defined as locally advanced disease or when patients cannot have or refuse surgery); 4. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L; 5. Platelets ≥ 100 x 109/L; 6. Hgb ≥ 9 g/dL; 7. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x \[Upper Limit of Normal (ULN)\]; 8. Bilirubin ≤ 1.5 x ULN; 9. GFR ≥ 30 mL/min; 10. Patient has no clinically significant abnormalities in urinalysis results; 11. Patient has acceptable coagulation status as indicated by a Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) within 15% of normal limits; 12. Eastern Cooperative Oncology Group (ECOG) ≤ 2 Exclusion Criteria: Subjects are ineligible for enrollment if they meet any of the following exclusion criteria: 1. Clinical evidence of deep vein thrombosis (DVT), pulmonary embolism (PE) or other known thromboembolic (TE) event present during the screening period; 2. Any prior history of cerebrovascular accident, transient ischemic attack, or pre-existing carotid artery disease. 3. Known allergy to hyaluronidase; 4. Current use of megestrol acetate (use within 10 days of Day 1); 5. Contraindication to heparin including prior heparin induced thrombocytopenia (HIT), recent CNS bleed; intracranial or spinal lesion at high risk for bleeding; severe platelet dysfunction; recent major operation at high risk for bleeding; underlying hemorrhagic coagulopathy; high risk for falls; potential need for spinal anesthesia/lumbar puncture; active bleeding; 6. Women currently pregnant or breastfeeding; 7. Intolerance to dexamethasone; 8. Inability to comply with study and follow-up procedures as judged by the Investigator; 9. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy; 10. Patient has known infection with HIV, hepatitis B, or hepatitis C; 11. Patient has a history of allergy or hypersensitivity to any of the agents they are supposed to receive (or to any of the excipients for those agents); 12. Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug, these can include New York Heart Association Functional Class ≥ 3, myocardial infarction within the past 12 months before screening, pre-existing atrial fibrillation, symptomatic COPD. 13. Patient is unwilling or unable to comply with study procedures.