Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma

Inclusion Criteria:

1. Patients with potentially resectable malignant pleural mesothelioma, IMIG stage I-III

2. Subject, age >/= 18 years

3. Any patient who is able to tolerate general anesthesia for the extended surgical
staging and the definitive surgical resection.

4. No prior chemotherapy for mesothelioma within the last 3 years

5. No prior radiation to the area of primary disease. Radiation to chest wall port sites
is acceptable.

6. No prior targeted biologic therapy (i.e. EGFR inhibitors, VEGF inhibitors) within the
last 3 years

7. Adequate Organ Function: a) Total bilirubin < 2.0 times the institutional Upper Limit
of Normal (ULN), b) Hepatic enzymes (AST, ALT ) c) Serum Na, K+, Mg2+, Phosphate and Ca2+>/= Lower Limit of Normal (LLN), d) Serum
Creatinine < 1.5 time the institutional ULN, e) Hemoglobin, Neutrophil count,
Platelets, PT, PTT all Grade 0-1

8. Ability to take oral medication (dasatinib must be swallowed whole)

9. Women of childbearing potential (WOCBP) must have: A negative serum or urine
pregnancy test (sensitivity study drug administration

10. Persons of reproductive potential must agree to use an adequate method of
contraception throughout treatment and for at least 4 weeks after study drug is
stopped

11. Signed written informed consent including HIPAA according to institutional guidelines

Exclusion Criteria:

1. Malignancy [other than the one treated in this study] which required radiotherapy or
systemic treatment within the past 3 years.

2. Prior therapies to be excluded: any prior chemotherapy or targeted biologic therapy
for mesothelioma used within the last 3 years

3. Concurrent medical condition which may increase the risk of toxicity, including: a)
Clinically-significant coagulation or platelet function disorder (e.g. known von
Willebrand's disease) b) Any disease which requires persistent anticoagulation
therapy (and the patient may not be taken off the anti-coagulation safely) with
coumadin, factor Xa inhibitors, or heparin (low-molecular weight, standard)

4. Cardiac Symptoms, consider the following: a) Uncontrolled angina, congestive heart
failure or MI within (6 months), b) Diagnosed congenital long QT syndrome: 1. Any
history of clinically significant ventricular arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or Torsades de pointes), 2. Prolonged QTc
interval on pre-entry electrocardiogram (> 450 msec), 3. Subjects with hypokalemia or
hypomagnesemia if it cannot be corrected

5. History of significant bleeding disorder unrelated to cancer, including: a) Diagnosed
congenital bleeding disorders (e.g., von Willebrand's disease), b) Diagnosed acquired
bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c)
Ongoing or recent (
6. Concomitant Medications, consider the following prohibitions: a) 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): A) quinidine,
procainamide, disopyramide, B) amiodarone, sotalol, ibutilide, dofetilide, C)
erythromycin, clarithromycin, D) chlorpromazine, haloperidol, mesoridazine,
thioridazine, pimozide E) cisapride, bepridil, droperidol, methadone, arsenic,
chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin,
lidoflazine. F) moxifloxacin, levofloxacin

7. The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not
recommended.The use of antacids should be considered in place of H2 blockers or
proton pump inhibitors in patients receiving dasatinib therapy.a)Patient agrees to
discontinue St. Johns Wort while receiving dasatinib therapy,b)Patient agrees that IV
bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to
risk of hypocalcemia,c)Patient may not be receiving any prohibited CYP3A4
inhibitors,d)Patient may not be receiving any alternative herbal remedies during the
dasatinib treatment period

8. Women: a) are 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,
b) have a positive pregnancy test at baseline, or c) are pregnant or breastfeeding,
d) Sexually active women of childbearing potential (WOCBP) must use an effective
method of birth control during the course of the study, in a manner such that risk of
failure is minimized.,

9. -continued from exclusion #8-: e) Prior to study enrollment, women of childbearing
potential must be advised of the importance of avoiding pregnancy during trial
participation and the potential risk factors for an unintentional pregnancy., f) All
WOCBP MUST have a negative pregnancy test prior to first receiving dasatinib. If the
pregnancy test is positive, the patient must not receive dasatinib and must not be
enrolled in the study.

10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness