Perioperative Therapy for Resectable and Borderline-Resectable Pancreatic Adenocarcinoma With Molecular Correlates
Condition: Pancreatic Cancer; Pancreatic Adenocarcinoma; Pancreas Ductal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Nab paclitaxel; Gemcitabine
Intervention description: Nab-paclitaxel and gemcitabine, for R-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.; Nab-paclitaxel and gemcitabine, for BR-PDAC patients, will be given in combination as neoadjuvant and adjuvant chemotherapy. Nab-paclitaxel will be administered by IV infusion at a dose of 125 mg/m2 over 30 minutes on Days 1, 8, and 15 of every 28-day cycle. Gemcitabine will be administered by IV infusion, immediately after the administration of nab-paclitaxel, at a dose of 1000 mg/m2 over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.
Intervention MeSH terms: Paclitaxel; Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 101 Years
Healthy volunteers: No
Keywords: Stereotactic Body Radiation Therapy; Perioperative Therapy; Resectable Pancreas Ductal Adenocarcinoma; Borderline Resectable Pancreas Ductal Adenocarcinoma; Nab-paclitaxel; Abraxane; Gemcitabine; Neoadjuvant Therapy; Adjuvant Therapy

Summary:

      The objective of this study is to estimate the R0 resection rate in patients with Resectable
      Pancreatic Ductal Adenocarcinoma (R-PDAC) as well as those with Resectable Pancreatic Ductal
      Adenocarcinoma (BR-PDAC) independently in response to neoadjuvant sequential therapy of
      combination nab-paclitaxel and gemcitabine followed by stereotactic body radiotherapy (SBRT).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed resectable or borderline resectable pancreatic
             adenocarcinoma.

          2. No evidence of distant metastasis representing stage IV metastatic disease.

          3. R-PDAC: No evidence of distant metastasis and tumor mass showing no extension to
             superior mesenteric artery (SMA) and hepatic artery. There must be a clearly defined
             fat plane between SMA and celiac axis. Patent superior mesenteric vein (SMV/portal
             vein (PV) with no distortion of venous architecture.

          4. BR-PDAC: defined as localized PDAC with 1 or more of the following features: a) an
             interface between the primary tumor and superior mesenteric vein (SMV)-portal vein
             (PV) measuring 180o or greater of the circumference of the vein wall, and/or b)
             short-segment occlusion of the SMV-PV with normal vein above and below the level of
             obstruction that is amenable to resection and venous reconstruction and/or c)
             short-segment interface of any degree between tumor and hepatic artery with normal
             artery proximal and distal to the interface that is amenable to resection and arterial
             reconstruction and/or d) an interface between the tumor and SMA or celiac trunk
             measuring less than 180o of the circumference of the artery wall.

          5. Age > 18 years old

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          7. Patients must have adequate bone marrow function:

               -  Platelets >100,000 cells/mm3

               -  Hemoglobin > 9.0 g/dL

               -  Absolute Neutrophil Count > 1,500 cells/mm3

          8. Patients must have adequate liver function:

               -  aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2.5 X upper
                  limit of normal

               -  Alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is
                  present in the absence of liver metastasis

               -  Total bilirubin < 1.5 mg/dL

          9. Patients must have adequate renal function: creatinine <1.5 mg/dL is recommended;
             however, institutional norms are acceptable. Creatinine within institutional limits of
             normal or creatinine clearance (CrCl) > 50 mL/min calculated using the Cockcroft-Gault
             equation.

         10. Women of childbearing potential and sexually active males must use an effective
             contraception method during treatment and for three months after completing treatment.

         11. Negative serum or urine β-human chorionic gonadotropin (hCG) pregnancy test at
             screening for patients of childbearing potential.

         12. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE 4.03).

         13. Ability to understand and willingness to sign a written informed consent.

        Exclusion Criteria:

          1. Patients with locally advanced surgically unresectable PDAC.

          2. Patients with evidence of distant metastatic PDAC.

          3. Prior chemotherapy or radiation therapy of any kind for treatment of pancreas
             adenocarcinoma.

          4. Prior major surgery within 4 weeks of starting study drug administration.

          5. Patient unable or not willing to perform all study related biopsies and blood draws
             for exploratory endpoints will not be enrolled on study as all study related
             procedures are mandatory.

          6. Concomitant treatment with full dose warfarin (coumadin) is NOT allowed. However,
             treatment with low molecular weight heparin (LMWH) (such as enoxaparin or dalteparin)
             or rivaroxaban is allowed. Patients on full dose warfarin (coumadin) must be
             transitioned to either LMWH or rivaroxaban prior to administration of any study
             related drugs.

          7. Recent or ongoing clinically significant gastrointestinal disorder (e.g.,
             malabsorption, bleeding, inflammation, emesis, diarrhea >grade 1).

          8. Patients with clinically significant cardiac disease (New York Heart Association
             Classification III or IV and cardiac arrhythmias not well controlled with medication),
             or myocardial infarction within the previous six months.

          9. Serious, uncontrolled, concurrent infection(s) requiring antibiotics.

         10. Pregnant or breastfeeding women: positive pregnancy test within 7 days of starting
             treatment.

         11. Treatment for other carcinomas within the last five years, except cured non-melanoma
             skin and treated in-situ cervical cancer.

         12. Participation in any investigational drug study within 4 weeks preceding the start of
             study treatment.

         13. Patients with external biliary drains.