Gemcitabine Hydrochloride, Nab-Paclitaxel, PEGPH20, and Rivaroxaban in Treating Patients with Stage III-IV Pancreatic Cancer That Cannot Be Removed by Surgery

Inclusion Criteria

• Signed, written Institutional Review Board (IRB)-approved informed consent form (ICF)
• Histologically confirmed locally advanced unresectable (stage III) or stage IV pancreatic ductal adenocarcinoma (PDAC)
• Measurable or evaluable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version (v)1.1
• For patients with locally advanced disease, no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of PDAC is permitted; for patients with metastatic disease, prior treatment for non-metastatic disease with 5-fluorouracil (5-FU) or gemcitabine administered as radiation sensitizer, or as a cytotoxic therapy, in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no >= grade 2 treatment-related toxicities are present
• Karnofsky performance status >= 70%
• Life expectancy >= 3 months
• A negative serum pregnancy test, if female of reproductive potential
• Total bilirubin =< 1.5 times upper limit of normal (ULN) (performed within 14 days prior to day 1)
• Aspartate aminotransferase ([AST]; serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ([ALT]; serum glutamic pyruvate transaminase [SGPT]) =< 2.5 times ULN, (if liver metastases are present, then =< 5 times ULN is allowed) (performed within 14 days prior to day 1)
• Serum creatinine =< 2.0 mg/dL or calculated creatinine clearance >= 60 mL/min (performed within 14 days prior to day 1)
• Serum albumin >= 3.0 g/dL (performed within 14 days prior to day 1)
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (performed within 14 days prior to day 1)
• Platelet count >= 100,000 plt/mm^3 (performed within 14 days prior to day 1)
• Hemoglobin >= 9 g/dL (performed within 14 days prior to day 1)
• Prothrombin time (PT)/international normalized ratio (INR) within normal limits (+/- 15%) or within therapeutic range if on warfarin (performed within 14 days prior to day 1)
• Partial thromboplastin time (PTT) within normal limits (+/- 15%) (performed within 14 days prior to day 1)
• 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

Exclusion Criteria

• Known central nervous system involvement or brain metastases
• New York Heart Association class III or IV cardiac disease or myocardial infarction within the past 12 months
• Known, clinically significant carotid artery disease
• Known, increased risk of bleeding
• Patients with TE event occurring > 6 months prior to enrollment and receiving active anticoagulation
• Patients with any prior history of arterial thrombosis or symptomatic pulmonary embolism
• Patients with current use of megestrol acetate (use within 10 days of day 1) will be excluded
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
• Known active infection with human immunodeficiency virus, hepatitis B, or hepatitis C
• Known allergy to hyaluronidase
• Patients with prosthetic heart valves
• Women currently pregnant or breastfeeding
• Intolerance of dexamethasone
• History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer or curatively-treated cervical carcinoma in-situ
• History of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
• Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that may render the subject at high risk for treatment complications
• Other unspecified reasons that, in the opinion of the investigator, make the subject unsuitable for the study
• Inability to comply with study and follow-up procedures as judged by the investigator