Alternative Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer

This research study is a Phase Ib clinical trial. It will assess the Safety, tolerability,
and feasibility of gemcitabine-nab paclitaxel alternating with nal-IRI/5FU/leucovorin
(NAPOLI) in de novo resectable and borderline resectable pancreatic cancer.

Subjects must have a newly diagnosed resectable or borderline resectable pancreatic ductal
cancer and meet all inclusion/exclusion criteria.

Treatment consists of 4 week treatment cycles. Nab-paclitaxel and gemcitabine will be
administered on days 1,8, and 15 with NAPOLI will be administered on days 1 and 15.

Inclusion Criteria:

1. Pathologically proven resectable or borderline resectable pancreatic cancer per
current NCCN criteria
(http://www.nccn.org/professionals/physician_gls/f_guidelines.asp).

2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0/1.

3. Adequate bone marrow reserves as evidenced by:

- absolute neutrophil count (ANC) ≥1,500 cells/μl without the use of hematopoietic
growth factors; and

- Platelet count ≥100,000 cells/μl; and

- Hemoglobin ≥9 g/dL (blood transfusions are permitted for patients with hemoglobin
levels below 9 g/dL).

4. Adequate hepatic function as evidenced by:

- Serum total bilirubin within normal range for the institution (biliary drainage
is allowed for biliary obstruction); and

- aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

- 2.5 x upper limit of normal (ULN) (≤5 x ULN is acceptable if liver
metastases are present).

5. Adequate renal function as evidenced by a serum creatinine ≤1.5 x ULN.

6. At least 18 years of age.

7. Women of child-bearing potential (defined as a 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 postmenopausal
for at least 24 consecutive months [i.e., has had menses at any time during the
preceding 24 consecutive months]) must: Either commit to true abstinence from
heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and
be able to comply with, effective contraception without interruption for 28 days prior
to starting study medications (including dose interruptions) and for 3 months after
last dose of study medication and Have a negative pregnancy test result at screening
and agree to ongoing pregnancy testing at the Investigator's discretion during the
course of the study. This applies even if the subject practices true abstinence from
heterosexual contact.

8. Male subjects must practice true abstinence or agree to use a condom during sexual
contact with a female of childbearing potential or a pregnant female while on
treatment (including during dose interruptions) with study medications and for 3
months following the last dose of study medication, even if he has undergone a
successful vasectomy.

Exclusion Criteria:

1. Prior therapy for pancreatic cancer (e.g., attempted surgery, chemotherapy, radiation
therapy).

2. Any contraindication to curative surgery.

3. History of any second malignancy in the last 5 years except in-situ cancer or basal or
squamous cell skin cancer. Subjects with history of other malignancies are eligible if
they have been continuously disease free for at least 5 years.

4. Severe arterial thromboembolic events (myocardial infarction, unstable angina
pectoris, stroke) less than 6 months before study participation.

5. New York Heart Association (NYHA) Class III or IV congestive heart failure,
ventricular arrhythmias or uncontrolled blood pressure.

6. Active infection or an unexplained fever >38.5°C during screening visit or on the
first scheduled day of dosing in each cycle which, in the Investigator's opinion,
might compromise the subject's participation in the trial or affect the study outcome.
Subjects with tumor fever may be enrolled at the discretion of the Investigator.

7. Known hypersensitivity to any of the components of nal-IRI, other liposomal products,
fluoropyrimidines or leucovorin.

8. Neuropathy > grade 1.

9. Investigational therapy administered within 4 weeks, or within a time interval less
than at least 5 half-lives of the investigational agent, whichever is longer, prior to
the first scheduled day of dosing in this study.

10. Any other medical or social condition deemed by the Investigator to be likely to
interfere with a subject's ability to sign informed consent, cooperate and/or
participate in the study in any way, or interfere with the interpretation of the
results.

11. Inability or unwillingness to provide written informed consent.

12. Patients who are not appropriate candidates for participation in this clinical study
for any other reason as determined by the investigator.