Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Dasatinib
Intervention description: Take tablets of Dasatinib by mouth once a day.
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Non-small Cell Lung Cancer

Summary:

      The main purpose of this study is to learn how patients with Advanced Non-Small Cell Lung
      Cancer (NSCLC) respond to the study drug Dasatinib. The study drug, Dasatinib, has been
      approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has
      not been approved for the treatment of other kinds of cancer. The use of Dasatinib in this
      study is considered experimental.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented diagnosis of NSCLC that is
             advanced/metastatic (Stage IIIB/IV).

          -  Performance Status (ECOG) 0-2

          -  Previous chemotherapy with the exception of dasatinib. Patients who have had any type
             of previous chemotherapy regimens for non-small cell lung cancer are eligible.

          -  Adequate Organ Function:

               -  Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN)

               -  Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN

               -  Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN)

               -  Serum Creatinine < 1.5 time the institutional ULN

               -  Hemoglobin, Neutrophil count, Platelets, prothrombin time (PT), partial
                  thromboplastin time (PTT) all Grade 0-1

          -  Ability to take oral medication

          -  Concomitant Medications:

               -  Agree to discontinue St. Johns Wort while receiving dasatinib therapy

               -  Agree that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib
                  therapy due to risk of hypocalcemia.

          -  Women of childbearing potential (WOCBP):

               -  A negative serum or urine pregnancy test within 72 hours prior to the start of
                  study drug administration

               -  Persons of reproductive potential must agree to use and utilize an adequate
                  method of contraception throughout treatment and for at least 4 weeks after study
                  drug is stopped Prior to study enrollment.

          -  Signed written informed consent including a HIPAA form according to institutional
             Guidelines

        Exclusion Criteria:

          -  No malignancy [other than the one treated in this study] which required radiotherapy
             or systemic treatment within the past 5 years.

          -  Prior dasatinib therapy.

          -  Concurrent medical condition which may increase the risk of toxicity, including:

               -  Patients with severe pulmonary disease that increases the risk of toxicity
                  related to dasatinib-induced pleural effusions. This includes chronic obstructive
                  pulmonary disease or pleural effusions (malignant or benign) requiring chronic
                  oxygen therapy or patients that have had prior pneumonectomy. Patients that have
                  a pulmonary embolism and require oxygen therapy will be excluded but not those
                  patients who have a pulmonary embolism but do not require oxygen therapy.
                  Patients with active pleural effusions not controlled with pleurodesis will be
                  excluded.

          -  Cardiac Symptoms; any of the following should be considered for exclusion:

               -  Uncontrolled angina, congestive heart failure or MI within (6 months)

               -  Diagnosed congenital long QT syndrome

               -  Any history of clinically significant ventricular arrhythmias (such as
                  ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)

               -  Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)

               -  Patients 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

               -  Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding

          -  Concomitant Medications, any of the following should be considered for exclusion:

               -  Category I drugs that are generally accepted to have a risk of causing Torsades
                  de Pointes including: (Patients must discontinue drug 7 days prior to starting
                  dasatinib)

                    1. quinidine, procainamide, disopyramide

                    2. amiodarone, sotalol, ibutilide, dofetilide

                    3. erythromycin, clarithromycin

                    4. chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

                    5. cisapride, bepridil, droperidol, methadone, arsenic, chloroquine,
                       domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin,
                       lidoflazine.

          -  Women:

               -  unwilling or unable to use an acceptable method to avoid pregnancy for the entire
                  study period and for at least 4 weeks after cessation of study drug,or

               -  have a positive pregnancy test at baseline

               -  pregnant or breastfeeding

          -  Prisoners or persons who are compulsorily detained (involuntarily incarcerated)for
             treatment of either a psychiatric or physical (e.g., infectious) illness

          -  Patients on systemic anticoagulation at risk of bleeding related to tumor biopsy that
             cannot be off anticoagulation per the discretion of their physician.