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

This phase II trial studies how well nab-paclitaxel and gemcitabine hydrochloride followed by radiation therapy before surgery work in treating patients with pancreatic cancer that can be removed by surgery. Chemotherapy drugs, such as nab-paclitaxel and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving nab-paclitaxel, gemcitabine hydrochloride, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PRIMARY OBJECTIVE:

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 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 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 1 year.

Eligibility Criteria:
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 because of the potential for pharmacokinetic interactions with chemotherapy; in addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy
* Subjects with plastic biliary stents will be excluded; metal biliary stents are allowed and will not be excluded