Phase II Neoadjuvant Chemotheraphy (Gemcitabine and Nab-Paclitaxel vs. mFOLFIRINOX) and Sterotatic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer
Condition: Borderline Resectable Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: gemcitabine/nab-paclitaxel; mFOLFIRINOX
Intervention description: three cycles of treatment in the gemcitabine/nab-paclitaxel; 6 cycles in the mFOLFIRINOX
Intervention MeSH terms: Paclitaxel; Gemcitabine; Fluorouracil; Oxaliplatin; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Borderline; Resectable; Pancreatic; Cancer; Neoadjuvant; Chemotheraphy; Gemcitabine; Nab-Paclitaxel; mFOFIRINOX; Sterotatic Body Radiation Therapy

Summary:

      This is a prospective, randomized phase II trial. Patients diagnosed with borderline
      resectable pancreatic adenocarcinoma will be randomly assigned to one of two treatment arms,
      either mFOLFIRINOX or gemcitabine and nab-paclitaxel. After three cycles of treatment in the
      gemcitabine/nab-paclitaxel arm and 6 cycles in the mFOLFIRINOX arm, patients will be restaged
      with CT scans and if they remain borderline resectable or have improvement of their disease
      They will then proceed to SBRT followed by surgical resection.
    

Eligibility criteria:

        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.