Phase II Neoadjuvant Chemotheraphy (Gemcitabine and Nab-Paclitaxel vs. mFOLFIRINOX) and Sterotatic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer

Inclusion Criteria:

All patients must meet the following criteria within 28 days of randomization (unless otherwise indicated) to be enrolled in the protocol:

• Histologically or cytologically proven adenocarcinoma of the pancreas. If the patient has mixed tumor with predominant adenocarcinoma pathology, they can be enrolled.
• Subjects will be staged according to the 2010 American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-4, N0 being eligible; and have a primary tumor of the pancreas (either pancreatic head, neck, uncinate process, or body/tail)
• The tumor must be deemed as being borderline resectable. Final CT confirmation of surgical staging/ eligibility will be at the discretion of the pancreatic surgeon of the patient.
• Disease is confined to locoregional site as confirmed by the CT and / or diagnostic staging laparoscopy to avoid occult peritoneal deposits. Diagnostic laproscopy will be only if absolutely required
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) on imaging studies CT
• Screening Endoscopic ultrasound if done prior to consent but within 6 weeks of expected randomization date it may be used.
• Karnofsky performance status greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance of 0-2.
• Age > 18
• Estimated life expectance > 12 weeks
• If female patient is of child bearing potential, she must have a negative serum pregnancy test (βhCG) documented up to 72hrs prior to administration of first study drug
• Patient has screening blood work performed which includes the following (should be drawn ≤ 14 days prior to randomization)
• absolute neutrophil count (ANC) > 1.5 x 109/L
• Platelet count ≥ 100000/mm3
• Hemoglobin (HgB) ≥ 9g/dL
• aspartate aminotransferase (AST),Alanine Aminotransferase (ALT)≤ 2.5 x upper limit of normal (ULN) Total Bilirubin ≤ ULN
• Serum Cr within normal limits (WNL)
• Coagulation studies with Prothrombin Time and International Normalized Ratio (PT/INR) and partial thromboplastin time (PTT) within normal limits (±15%). • Patient has a urinalysis obtained (≤14 days prior to randomization) and the results are deemed not clinically significant by the investigator.
• Patient has no evidence of jaundice at the time of enrolment. If stent is required to alleviate jaundice, it should be metallic. If patient has a previously placed stent and this is plastic, this should be changed to metallic.
• Patient's pain symptoms have remained stable with no adjustment to analgesics within 7 days prior to randomization. Patient must be able to swallow entreat medications with no requirement for a feeding tube. Patient's must not have intractable nausea or vomiting which prohibits the patient from oral medications
• Diabetes must be controlled prior to enrollment
• Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating radiation oncologist

Exclusion Criteria:

• Ineligible Histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas
• Evidence of distant metastasis on upright chest x-ray, CT or other staging studies
• Subjects with recurrent disease
• Prior radiation therapy to the upper abdomen or liver at the discretion of the treating radiation oncologist could impair delivery of the prescribed radiation treatment
• Prior chemotherapy
• Subjects in their reproductive age who are breast feeding or have a positive pregnancy test
• Any co-morbid condition of sufficient severity to limit full compliance with the protocol per assessment by the individual treating physician
• Concurrent active infection
• Previous or current malignancies of other histologies within the last 3 yrs prior to randomization; with the exception of cervical cancer in situ, adequately treated basal cell or squamous cell carcinoma of skin or treated low risk prostate cancer
• Patient with known historical or active infection with HIV, Hepatitis B or Hepatitis C
• Patient who has undergone recent major surgery, other than diagnostic surgical procedure within 4 weeks prior to randomization.
• Patient who has a history of allergy or hypersensitivity to any of the study drugs.
• Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
• Patients with greater than 2 screening peripheral neuropathy.