Phase II Study of 5-FU, Oxaliplatin Plus Dasatinib in Metastatic Pancreatic Adenocarcinoma
Condition: Pancreatic Cancer Metastatic
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms
Intervention: Dasatinib; mFOLFOX6
Intervention description: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle; mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Pancreatic Cancer; Adenocarcinoma

Summary:

      The purpose of this research study is to determine if the study drug, dasatinib, given in
      combination with 5-Fluorouracil, leucovorin and oxaliplatin (FOLFOX) will work against
      metastatic pancreatic cancer.

      Dasatinib is a Food and Drug Administration (FDA) approved drug for treating chronic
      myelogenous leukemia and acute lymphoblastic leukemia, however it is not currently approved
      for use in the treatment of pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pancreatic adenocarcinoma with evidence of metastatic disease on imaging

          -  Measurable disease (per RECIST 1.1)

          -  ECOG Performance Status 0-2

          -  No prior chemotherapy or radiotherapy for metastatic pancreatic cancer. Patients may
             have received prior treatment for non-metastatic disease; however the diagnosis of
             metastatic disease must have been made more than 6 months after completion of
             treatment.

          -  Patients may have a history of other malignancies if there is no current evidence of
             persistent or recurrent disease and they are not undergoing any active therapy
             (including hormonal)

          -  Patent biliary system

          -  Patients receiving anti-coagulation treatment with an agent such as Coumadin or
             heparin may be allowed to participate, provided they are on stable anti-coagulation
             therapy with no active bleeding and have no condition that carries a high risk of
             bleeding

          -  Adequate organ and marrow function

          -  Ability to take oral medication (dasatinib must be swallowed whole)

          -  Patient agrees to discontinue prohibited concomitant medications

          -  Age > 18 years

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception throughout the study and for at least 4 weeks after the last dose of
             study drug.

          -  A male subject of fathering potential must use an adequate method of contraception
             throughout the study and for at least 4 weeks after the last dose of study drug.

        Exclusion Criteria:

          -  WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
             the entire study period and for at least 4 weeks after the last dose of study drug.
             Women who are pregnant or breastfeeding and sexually active fertile men not using
             effective birth control if their partners are WOCBP are also excluded.

          -  History of known brain metastases or carcinomatous meningitis

          -  Recent major surgery (within 4 weeks) or minor surgery (within 2 weeks), excluding
             placement of a vascular access device or biliary stent

          -  Uncontrolled diabetes

          -  Any sensory neuropathy > grade 1 at baseline

          -  Serious active or uncontrolled infection

          -  Concurrent medical condition which may increase the risk of toxicity including
             clinically significant pleural or pericardial effusion, patients with known DPD
             deficiency or patients with a history of allergic reactions attributed to oxaliplatin,
             5-FU or leucovorin.

          -  Cardiac Symptoms including unstable angina or stable angina markedly limiting ordinary
             physical activity, NYHA class III or IV congestive heart failure, myocardial
             infarction or stroke within 6 months of study enrollment, diagnosed congenital long QT
             syndrome, any history of clinically significant ventricular arrhythmias, prolonged QTc
             interval on pre-entry ECG or clinically significant peripheral vascular disease.

          -  Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to
             dasatinib administration

          -  History of significant bleeding disorder unrelated to cancer, including diagnosed
             congenital bleeding disorders, diagnosed acquired bleeding disorder within one year or
             ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.

          -  History of any other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of protocol therapy, might affect the interpretation of the
             results of the study, or that puts the subject at high risk for treatment
             complications.

          -  Use of category I drugs that are generally accepted to have a risk of causing Torsades
             de Pointes

          -  Use of potent CYP3A4 inhibitors that significantly increase dasatinib exposure

          -  Prisoners or subjects who are involuntarily incarcerated

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness

          -  Inability to comply with study and/or follow-up procedures