A Phase II Study of siG12D LODER in Combination With Chemotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

Inclusion Criteria:

• Provide written informed consent and be between the ages of 18 and up.
• Have an unresectable, locally advanced diagnosed adenocarcinoma of the pancreas. Or patients with a tumor who are not planning 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 in accordance with treating physician recommendation.
• 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 an ECOG performance status of ≤ 1
• 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 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, 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. Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as follows:

CT-scan {> 10 mm} Lymph node short axis{ > 15 mm}

All radiology studies must be performed within 28 days prior to registration (35 days if negative).

Exclusion Criteria:

• New York Heart Association (NYHA) Class III or IV, cardiac disease,myocardial infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
• Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months) or any other metastases
• Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancers from which the subject has been disease-free for at least 5 years
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Treatment of pancreatic cancer with surgery or radiation therapy prior to study entry
• Prior therapy with an hypoxic cytotoxin
• Subjects who participated in an investigational drug or device study within 28 days prior to study entry
• Known infection with HIV, hepatitis B virus, or hepatitis C virus
• Females who are pregnant or breast-feeding
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
• Unwillingness or inability to comply with the study protocol for any reason