Efficacy and Safety of BC-819 and Gemcitabine in Patients With Locally Advanced Pancreatic Adenocarcinoma (LAPC-BC-819)

Inclusion Criteria:

1. Males or females > 18 years of age
2. If female, must not be pregnant or nursing; women of child-bearing potential must practice a medically approved method of contraception
3. If male, must practice a medically approved method of contraception if have a partner of childbearing potential
4. Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
5. Locally advanced pancreatic cancer (LAPC) that is clinically unresectable as defined in the NCCN Guidelines
6. Karnofsky performance status (KPS) ≥ 70% at baseline

7. Adequate hematological, renal, and hepatic function

   • Platelet count ≥ 100,000/mm3
   • Absolute neutrophil count (ANC) ≥ 1500/mm3
   • Hemoglobin ≥ 10.0 g/dL (may be achieved by transfusion)
   • Creatinine (≤ 1.5 x ULN)
   • ALT, AST (≤ 1.5 x ULN)
   • Total Bilirubin (≤ 1.5 x ULN)
8. Have a target tumor lesion in the pancreas ≤ 6 cm in diameter that is accessible for intratumoral administration by EUS guidance as determined by the physician performing the EUS injection
9. Have a biopsy specimen that is positive for H19 expression (grade 2 or greater staining determined by a pathologist). H19 expression can be determined based on a biopsy specimen collected before study participation, if available.
10. No prior diagnosis of malignancy within 3 years except for curatively treated non-melanoma skin or in situ malignancies
11. Able to comply with the protocol procedures
12. Able and willing to provide written (signed) Informed Consent to participate in the study

Exclusion Criteria:

1. Have distant metastatic spread (such as liver or lung metastases), peritoneal spread or malignant ascites. Regional lymph node involvement may be considered in accordance with the PI's judgment
2. Received any prior therapy for the treatment of pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational, other than up to4 single doses of gemcitabine chemotherapy.Patients who received prior gemcitabine will only be eligible, if they enter the study without evidence of disease progression.
3. Known human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B virus (HBV) infection
4. Have clinically significant pancreatitis within 12 weeks of treatment
5. Have a clinical history of significant coagulopathy
6. Have a medical condition contraindicated for endoscopic-guided delivery and/or for IV administration of Gemcitabine or any intercurrent medical illness or other medical condition that would in the judgment of the investigator compromise patient safety or the objectives of the study
7. Have participated in any experimental therapeutic research study with an unapproved drug within 4 weeks of the screening visit
8. Patients who require ongoing anticoagulation for pre-existing conditions, e.g., thrombophlebitis, pulmonary embolus or atrial fibrillation