Targeted Delivery of OncoVEX GM-CSF by Endoscopic Ultrasound (EUS)-Guided Fine Needle Injection (FNI) in Patients With Irresectable Pancreatic Cancer: A Pilot Multinational Experiment on Safety and Proof of Concept

Inclusion Criteria:

- cytological or histological proof of adenocarcinoma of the pancreas

- unresectable, locally advanced disease (isolated liver metastases are permitted)

- tumors of at least 1 cm diameter at screening

- measurable disease using RECIST criteria

- failure of either standard therapy, OR any one of the following:

- no alternative therapeutic of higher curative potential is available;

- investigator determination that patient could not tolerate alternative
therapeutic due to unacceptable toxicity; or,

- patient refusal to be treated with available alternative therapeutic

- age > 18 years

- life expectancy > 3 months

- adequate bone marrow function as indicated by:

- WBC ≥ 3.0 x 109/L

- platelets ≥ 100 x 109/L

- hemoglobin ≥ 8.5 gm/dL

- adequate liver function as indicated by:

- bilirubin < 1.5 x upper limit of normal (ULN)

- ALT or AST < 5 x ULN in case of presence of liver metastasis

- ALT or AST < 2.5 x ULN in case of absence of liver metastasis

- adequate renal function as indicated by a serum creatinine level < 1.5 x ULN.

- adequate hemostasis indicated by INR ≤ 1.5

- mentally, physically and geographically able to undergo treatment and follow-up

- provided written informed consent

- first patient in each cohort only: seropositive for HSV1

Exclusion Criteria:

- history of other malignancy within two years prior to screening, except for prostate
cancer (T1c, T2ab with definitive treatment, PSA < 1 ng/ml, and without ongoing
hormone suppression) or adequately treated in situ carcinoma of the cervix, basal
cell carcinoma, or squamous cell carcinoma of the skin

- cystic form of pancreatic cancer; microcystic disease may be eligible upon discussion
with Medical Monitor

- CTCAE v3 grade 2 or greater clinical pancreatitis within 8 weeks prior to dosing with
OncoVEXGM CSF

- other than metastases limited to the liver, imaging evidence of metastatic disease to
any other organ or tissue

- any serious concomitant systemic disorder that would compromise the safety of the
patient, at the discretion of the investigator

- evidence of compromised immune function including but not limited to:

- clinically significant absolute lymphocyte count < Lower Limit of Normal (LLN)

- known HIV, acute or chronic active hepatitis B, or hepatitis C infection;

- concurrently taking HIV antiviral medications (e.g. protease inhibitors, AZT,
etc.)

- received IV, IM or SC human gamma globulin within 6 months prior to dosing with
OncoVEXGM CSF

- patients taking immunosuppressive agents (e.g. cyclosporine, tacrolimus, or oral or
systemic corticosteroids at a dose of >10mg/day of prednisone or equivalent).

- pregnancy, lactation or lack of effective contraception in women of child-bearing
potential (e.g., not post menopausal for > 2 years, or had tubal ligation); lack of
effective contraception in men if the partner is of child-bearing potential; women
must have been practicing an effective contraceptive method for at least three months
prior to entry in to the trial (hormonal contraception or intrauterine device in
conjunction with a barrier method); men must use a condom or be surgically sterilized

- patients with active bacterial or viral infections that require treatment with
systemic antibiotics or antiviral agents within 2 weeks prior to the first dose of
OncoVEXGM-CSF); (note: patients with active cold sores or other HSV1 infections must
wait until those lesions have crusted over before receiving OncoVEXGM-CSF)

- surgery requiring general or spinal anesthesia within four weeks prior to dosing with
OncoVEXGM CSF

- Treatment with an investigational agent within 4 weeks prior to the first dose of
OncoVEXGM CSF

- serum CA19.9 levels > 3000 U/mL at screening

- evidence of ascites on screening abdominal CT scan