Nab-paclitaxel and Gemcitabine Hydrochloride Followed by Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine the R0 (complete resection) resection rate for subjects with borderline
resectable or lymph node positive pancreatic adenocarcinoma treated with a multimodality
neoadjuvant therapy of preoperative gemcitabine (gemcitabine hydrochloride) and ABRAXANE
(nab-paclitaxel) followed by 5-fluorouracil (fluorouracil) based image-guided
intensity-modulated radiation therapy (IG-IMRT) chemoradiotherapy.

SECONDARY OBJECTIVES:

I. To determine 1-year relapse-free survival rate with the investigational protocol.

II. To determine 1-year and 2-year overall survival rates. III. To assess response rate by
imaging (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and pathologic analysis.

IV. To assess the toxicity and safety according to Common Terminology Criteria for Adverse
Events version 4.0 (CTCAE v4.0) criteria.

OUTLINE:

PRE-OPERATIVE (NEOADJUVANT) CHEMOTHERAPY: Patients receive nab-paclitaxel intravenously (IV)
over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15.
Treatment repeats every 28 days for 2 courses in the absence of disease progression or
unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo
IG-IMRT 5 days a week for 28 fractions and receive fluorouracil IV continuously on days 1-7
for 6 weeks.

SURGICAL RESECTION: Patients undergo surgery 4-10 weeks after the last dose of
chemoradiation.

POST-OPERATIVE (ADUJUVANT) CHEMOTHERAPY: Beginning within 8-12 weeks after surgery, patients
receive nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 30 minutes on
days 1, 8, and 15. Treatment repeats every 28 days for 4 additional courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 3 years and
then every 24 weeks for 2 years.

Inclusion Criteria:

- Subjects must have histologically or cytologically confirmed adenocarcinoma of the
pancreas

- Tumors must be localized (non-metastatic) and classified as borderline resectable
according to Americas Hepato-Pancreato-Biliary Association (AHPBA)/Society of Surgical
Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT) consensus criteria
or be clinically node-positive via computed tomography (CT) or endoscopic ultrasound

- AHPBA/SSO/SSAT criteria (any one of the following):

- Tumor-associated deformity of the SMV (superior mesenteric vein) or PV
(portal vein)

- Abutment of the SMV or PV >= 180 degrees

- Short-segment occlusion of the SMV or PV amenable to resection and venous
reconstruction

- Short-segment involvement of the hepatic artery or its branches amenable to
resection and reconstruction

- Abutment of the superior mesenteric artery (SMA) < 180 degrees

- Subjects must have measurable disease (by RECIST 1.1), defined as at least one lesion
that can be accurately measured in at least one dimension (longest diameter to be
recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with
conventional techniques or as >= 10 mm with spiral CT scan

- No prior therapy for pancreatic cancer, including chemotherapy, radiation therapy,
definitive surgery or investigational therapy

- Members of all races and ethnic groups will be included

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1

- Absolute neutrophil count >= 1.5 K/cu mm

- Platelets >= 100 K/cu mm

- Hemoglobin >= 9.0 g/dL

- Total bilirubin =< 1.25 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal

- Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min

- No active prior malignancy within 3 years of registration (with the exception of
non-melanoma skin cancer, in-situ cancers, or Rai stage 0 chronic lymphocytic leukemia
[CLL]); if patient is disease free from a prior malignancy between 3-5 years, special
consideration can be requested; in these cases, if the risk of recurrence at 5 years
is less than 20%, and in the opinion of the investigator the prior malignancy will not
affect the patient's outcome in light of newly diagnosed pancreatic cancer, the
patient may be eligible; this will require principle investigator (PI) review and
approval on a case by case basis, and approval will be documented in the medical
record; all patients who have been disease free from a prior malignancy for at least 5
years will be eligible

- No baseline peripheral sensory neuropathy >= grade 2

- Women of child-bearing potential and men must be willing to use adequate contraception
during the entire study and for 8 weeks following completion of all chemotherapy on
study; this includes hormonal or barrier method, or abstinence

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Subjects with locally advanced, unresectable primary tumors will not be eligible

- This includes any of the following:

- Abutment of the SMA >= 180 degrees

- Occlusion of the SMV or PV with insufficient normal vein above and below
with which to perform venous reconstruction

- Involvement of the hepatic artery with insufficient artery proximal and
distal to perform reconstruction

- Any prior therapy (chemotherapy, radiation or surgery) for pancreatic adenocarcinoma
other than biliary decompression

- Subjects who are receiving any other investigational agents

- Subjects with known metastases

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ABRAXANE or other agents used in the study

- Active infection requiring intravenous antibiotics at the time of registration

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- History of interstitial lung disease, idiopathic pulmonary fibrosis, silicosis,
sarcoidosis or connective tissue disorders (including rheumatoid arthritis and
systemic lupus erythematosus)

- Pregnant or breastfeeding women are excluded from this study

- Subjects known to be human immunodeficiency virus (HIV)-positive, including those on
combination antiretroviral therapy, are ineligible

- Subjects with plastic biliary stents will be excluded; metal biliary stents are
allowed and will not be excluded