Pancreas Cancer: Molecular Profiling as a Guide to Therapy Before and After Surgery ("Personalized Medicine")
Condition: Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Milestone 1: Targeted chemotherapy prior to surgery; Milestone 2: Chemoradiotherapy (cXRT); Milestone 3: Targeted chemotherapy prior to surgery; Milestone 3: Chemoradiotherapy (cXRT); Milestone 4: standard FOLFIRINOX chemotherapy prior to surgery; Milestone 4: Chemoradiotherapy (cXRT); Milestone 5: Targeted chemotherapy after surgery; Milestone 5: Chemoradiotherapy (cXRT); Milestone 6: Gemcitabine after surgery; Milestone 6: Chemoradiotherapy (cXRT); Milestone 7: Chemoradiotherapy (cXRT); Milestone 8: Targeted chemotherapy after surgery; Milestone 9: Gemcitabine after surgery; Milestone 10: No additional therapy after surgery
Intervention description: The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.; A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or intensity-modulated radiation therapy (IMRT) techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).; The molecular profile from the biopsy before surgery will point to a particular chemotherapy treatment.; A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).; A biopsy of the borderline tumor does not provide a molecular profile that can be used to target treatment. The treatment will be standard FOLFIRINOX chemotherapy regimen.; A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).; The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.; A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).; Chemotherapy treatment with Gemcitabine.; A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).; A radio-sensitizing chemotherapy agent (either Gemcitabine or Capecitabine) will be given. Using 3D conformal or IMRT techniques, patients will receive a total dose of 50.4 Gy prescribed to the 95% isodose at 1.8 Gy/fraction (28 fractions).; The molecular profile from the surgical specimen will point to a particular chemotherapy treatment.; Chemotherapy treatment with Gemcitabine.; The molecular profile of the tumor that was removed during surgery points to a lack of treatment affect for available therapies. No additional therapy is recommended.
Intervention MeSH terms: Leucovorin; Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; Capecitabine; Fluorouracil; Oxaliplatin; Irinotecan; Cisplatin; Folfirinox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 229.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pancreas; adenocarcinoma; molecular profile; molecular profiling; pancreatic cancer; pancreas cancer; cancer; molecular target; pancreas head; pancreas neck; pancreas uncinate; pancreas body; pancreas tail

Summary:

      In this clinical trial, if the doctor knows or suspects that a growth in the pancreas is
      cancer (adenocarcinoma), then a sample of the growth is tested (the test is called molecular
      profiling). The results of the test are used by the doctor to recommend therapy (chemotherapy
      and radiation therapy) that the patient will receive before having surgery to remove the
      adenocarcinoma. When the patient goes to surgery, the adenocarcinoma that is removed is
      tested again. The results of that test are used to guide the choice of therapy after surgery.

      The chemotherapy drugs and the radiation therapy used in this clinical trial are already
      approved for treatment of pancreas cancer. This trial is intended to establish which
      treatment is best for a specific patient, based on test results from that patient's actual
      adenocarcinoma. In the past, the decision as to which treatment the patient will receive was
      not based on testing of the actual adenocarcinoma.

      See treatment pathways at http://www.mcw.edu/surgery/patientinfo/Pancreatic-Cancer-Trial.htm.

      Hypothesis: Resectability rate, overall survival rate and progression-free survival in
      subjects with adenocarcinoma of the pancreas will be superior for who receive targeted
      "personalized" therapy.
    

Eligibility criteria:

        Inclusion criteria:

          -  18 years of age or older

          -  Able to understand and provide written informed consent

          -  Diagnosis of adenocarcinoma of the pancreas or high suspicion of adenocarcinoma of the
             pancreas based on CT and MRI findings as detailed below by "Definition of...."

        Treatment Eligibility Criteria:

          -  Have an Eastern Cooperative Oncology Group performance status less than or equal to 2

          -  Have biopsy-proven resectable or borderline resectable adenocarcinoma of the pancreas

          -  Have adequate organ and bone marrow function as defined by:

               -  total leukocytes greater than or equal to 3 x1000/μL

               -  absolute neutrophil count (ANC) > or equal to 1.5x 1000/μL

               -  hemoglobin > or equal to 9 g/dL

               -  platelets > or equal to 100 x 1000/μL

               -  creatinine clearance >60 mL/min or creatinine < or equal to 1.5 mg/dL

               -  bilirubin < or equal to 2 mg/dL or >2 and declining as described in the protocol

               -  aspartate transaminases (AST/SGOT) < or equal to3 x upper limit of normal (ULN)

               -  alanine transaminases (ALT/SGPT) < or equal to 3 x ULN

          -  Female patients must be post menopausal for > 1 year, surgically sterile, or have a
             negative pregnancy test and used at least one form of contraception for 4 weeks prior
             to Day 1 of the study, during study treatment and during the first 4 months after
             study treatment is discontinued. Male patients must be surgically sterile or use
             barrier contraception during the study and for 4 months after the last dose of any
             study drug.

        Definition of Resectable Pancreatic Cancer includes:

          -  No evidence of extra-pancreatic disease

          -  No evidence of tumor-arterial abutment (celiac, superior mesenteric artery or hepatic
             artery)

          -  If tumor induced narrowing of the superior mesenteric vein, portal vein or superior
             mesenteric-portal vein confluence is present it must be <50% of the diameter of the
             vessel

          -  Ca19-9 <5000, when bilirubin is <2 (or >2 and declining as described in the protocol)

        Definition of Borderline Resectable Pancreatic Cancer to include at least one of the
        following:

          -  Tumor abutment < or equal to 180 degrees of the superior mesenteric artery or celiac
             axis

          -  Tumor abutment or encasement (>180 degrees) of a short segment of the hepatic artery

          -  Tumor induced narrowing of superior mesenteric vein, portal vein or superior
             mesenteric-portal vein of >50% of the diameter of the vessel.

          -  Short segment occlusion of the superior mesenteric vein, portal vein or superior
             mesenteric-portal vein confluence with a suitable portal vein above and superior
             mesenteric vein below, for reconstruction

          -  CT or MRI findings suspicious for, but not diagnostic of, metastatic disease (based on
             multidisciplinary assessment at the Medical College of Wisconsin weekly pancreatic
             cancer conference)

          -  Biopsy proven N1 disease (regional lymph nodes involved) from pre-referral biopsy or
             endoscopic ultrasound-guided fine needle aspirate

          -  Resectable tumor and cancer antigen 19-9 (CA19-9) >5000

        Exclusion Criteria:

        Any patient with one or more of the following will be excluded:

          -  Have received chemotherapy or chemoradiation within 5 years prior of study enrollment

          -  Have any previous history of another malignancy (other than cured basal or squamous
             cell carcinoma of the skin or cured in-situ carcinoma of the cervix) within 5 years of
             study enrollment

          -  Uncontrolled comorbidities including, but not limited to, ongoing or active serious
             infection, symptomatic congestive heart failure, unstable angina, unstable cardiac
             arrhythmias, psychiatric illness, excessive obesity, or situations that would limit
             compliance with the study requirements or the ability to willingly give written
             informed consent

          -  Known human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection

          -  Pregnant or breast-feeding patients or any patient with child-bearing potential not
             using contraception 4 weeks prior to, during and 4 months after study treatment is
             discontinued