Neoadjuvant GMCI Plus mFOLFIRINOX and Chemoradiation for Non-Metastatic Pancreatic Adenocarcinoma

The current protocol is designed to delivery multiple courses of GMCI timed with a series of
neoadjuvant debulking therapies- modified FOLFIRINOX (mFX) chemotherapy followed by
gemcitabine-radiation (GR) followed by surgery- to capitalize on the synergies with the
different treatment modalities.

This protocol includes two phases: Phase 1b followed by Phase 2. The Phase 1b evaluates the
safety and feasibility of mFX+GR+surgery in combination with GMCI. Patients will be enrolled
on the Phase 1b based on the definition of dose limiting toxicity (DLT), waiting periods and
stopping rules described in the protocol. The Phase 2 is a randomized study comparing a test
group receiving GMCI added to mFX+GR+surgery to a control arm receiving mFX+GR followed by
surgery.

Inclusion Criteria:

- Pathological diagnosis of pancreatic adenocarcinoma before first treatment but may be
enrolled with presumed diagnosis based on clinical and radiologic evaluation with
confirmation made by biopsy at time of EUS prior to AdV-tk injection

- Patients must be deemed to be in adequate health to undergo major surgery
(pancreaticoduodenectomy)

- Tumor accessible for injection that is classified as borderline-resectable or locally
advanced but considered potentially resectable after central review by surgical
investigators. Resection may include major vascular resection with reconstruction as
needed.

- Age 18-76 years

- Performance status ECOG 0-1

- SGOT (AST)<3x upper limit of normal

- Total bilirubin ≤2mg/dl

- Creatinine<2mg/dl

- Calculated creatinine clearance >30ml/m

- WBC>3000/mm3

- Absolute neutrophil count (ANC)>1500/mm3

- Platelets>100,000/mm3

- Hemoglobin > 9 g/dL.

- Patients must give study specific informed consent prior to enrollment

Exclusion Criteria:

- Baseline peripheral sensory neuropathy ≥ grade 2

- Primary hepatic dysfunction including known cirrhosis or active hepatitis. Patients
with biliary obstruction must be stented prior to initiating treatment.

- Evidence of clinically significant pancreatitis as determined by the investigator

- Evidence of significant ascites as determined by the investigator

- Patients on systemic corticosteroids (>10 mg prednisone per day or equivalent) or
other systemic immunosuppressive drugs

- Known to be HIV+

- Pregnant or breast-feeding. Female patients of childbearing age must have negative
serum or urine pregnancy test within 1 week of beginning therapy.

- Other current malignancy (except squamous or basal cell skin cancers)

- Prior abdominal radiation therapy or prior chemotherapy for pancreatic cancer

- Other serious co-morbid illness or compromised organ function

- Known sensitivity or allergic reactions to acyclovir or valacyclovir