Study of FOLFIRINOX Electrochemotherapy in the Treatment of Pancreatic Adenocarcinoma

This is a phase I dose escalation trial using a 3 + 3 dose escalation scheme to evaluate the
maximum tolerated field strength dose of administered irreversible electroporation in
combination with chemotherapy. During the first cycle of chemotherapy, patients will receive
electroporation of the primary pancreatic tumor prior to administration of chemotherapy with
FOLFIRINOX. The schedule of administration of FOLFIRINOX will be administered as per
standard of care. The investigators will use non-invasive dynamic magnetic resonance imaging
and magnetic resonance spectroscopy to detect and describe changes within the tumor. Safety
will be determined by assessing the number of class three or higher toxicity events in
cohorts of 6 patients at progressively higher electroporation voltages. The maximum
tolerated dose (MTD) will be defined as one voltage level less than the voltage at which two
or more patients out of six total patients have a class three or higher toxicity event.

Inclusion Criteria:

- Histologically or cytologically proven pancreatic carcinoma which is safely
accessible by percutaneous methods;

- Locally advanced un-resectable pancreatic adenocarcinoma;

- At least one measurable lesion according to Response Evaluation Criteria In Solid
Tumors (RECIST) criteria (longest diameter >=20 mm using conventional techniques or
>=10 mm with spiral CT or MRI scan);

- WHO performance status (PS) < 2 or Eastern Cooperative Oncology Group < 2;

- Age >18;

- Life expectancy > 3 months;

- No history of gastric or esophageal varices;

- No active, uncontrolled infection;

- All patients must have adequate physiologic (hematologic, renal and hepatic) reserves
as evidenced by: neutrophil count >1500/mL; platelet count >100,000/mL; serum
creatinine <1.5x the upper limit of normal (ULN) value; serum glutamic-pyruvic
transaminase (SGPT) <2.5 x ULN and bilirubin <1.5 x ULN functions

- Pain and biliary obstruction controlled before the start of the study

- Absence of psychological, familial, sociological, or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;

- Women of childbearing potential (defined as sexually mature woman who 1) has not
undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy
[the surgical removal of both ovaries] or 2) has not been naturally post-menopausal
for at last 24 consecutive months) must have a negative pregnancy test prior to
starting therapy. Men and women of childbearing potential must be willing to use
effective contraceptive while on treatment and for a reasonable period thereafter.

Exclusion Criteria:

- Prior chemotherapy with FOLFIRINOX;

- Prior history of pancreatic electroporation;

- Untreatable contrast allergy;

- History of allergy or hypersensitivity to gemcitabine, nab-paclitaxel, or any of the
excipients;

- Presence of metal biliary stent;

- Psychosis or seizures;

- Evidence of serious gastrointestinal bleeding or bowel obstruction;

- Pregnant or lactating women;

- Women of childbearing potential who are not using adequate protection;

- Inability to tolerate MRI imaging