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.