Phase I - Escalating Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Locally Advanced Adenocarcinoma of the Pancreas, and a Single Dose Study of siG12D LODER (Local Drug EluteR) in Patients With Non-operable Adenocarcinoma of the Pancreas

Inclusion Criteria: Phase 0: Provide written informed consent and be between the ages of 18 and up, inclusive. * Patient that is diagnosed as respectable locally pancreatic tumor * Have a target tumor accessible for intratumoral administration by EUS (Endoscopic Ultrasound) guidance as determined by the physician performing the EUS guided LODER insertion. * Have a Karnofsky performance status of ≥ 70%. * Have a life expectancy of \>= 3 months. * If female and of child-bearing potential, have a negative serum pregnancy test during screening. * Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment. * Have serum creatinine \< 2.0 mg/dL, , PT, - INR \< 1.5 absolute neutrophil count (ANC) \> 1,000 x 103 cells/mL, platelets ≥ 75,000/mL, and hemoglobin \>= 10 mg/dL. * Have screening procedures completed within 2 weeks of starting treatment. * No other malignancy present that would interfere with the current intervention. * Have measurable disease. Phase I * Provide written informed consent and be between the ages of 18 and up. * Have an unresectable, locally advanced diagnosed or highly suspected adenocarcinoma of the pancreas. Or patients with a tumor and are not planed to undergo surgery due to a high surgical risk (e.g. coagulopathy or severe congestive heart failure). * Allocated to receive standard of care chemo as first line treatment. * Have a target tumor that is accessible for intratumoral administration by PTA or EUS guidance as determined by the radiologist/gastroenterologist performing the PTA/EUS injection. * Have a Karnofsky performance status of ≥ 70%. * Have a life expectancy of \>= 3 months. * If female and of child-bearing potential, have a negative serum pregnancy test during screening. * Agree to use of a barrier method of contraception if sexually active (both men and women) from the time of administration of the first treatment and for at least 8 weeks after treatment. * Have serum creatinine \< 2.0 mg/dL, PT - INR \< 1.5, absolute neutrophil count (ANC) \> 1,000 x 103 cells/mL, platelets ≥ 75,000/mL, and hemoglobin \>= 10 mg/dL. * Have screening procedures completed within 4 weeks of starting treatment. * No other malignancy present that would interfere with the current intervention. * Have measurable disease. Exclusion Criteria: Phase 0: * Have distant metastasis spread (such as liver or lung, or lymph nodes metastases), peritoneal spread or malignant sites. * Have clinically significant pancreatitis within 12 weeks of treatment. * If female, be breast feeding. * Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery 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. * Have a history of bleeding coagulopathy. * Have participated in any therapeutic research study within the last 4 weeks. Phase I: * Have distant metastatic spread (such as liver, lung, or lymph nodes metastases), peritoneal spread or malignant sites. * Have clinically significant pancreatitis within 12 weeks of treatment. * If female, be breast feeding. * Have a medical condition contraindicated for both percutaneous- and endoscopic- guided delivery 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. * Have a history of bleeding coagulopathy. * Have participated in any therapeutic research study within the last 4 weeks.