Dasatinib in Resectable Malignant Pleural Mesothelioma

The Study Drug Dasatinib is designed to decrease the activity of one or more proteins that
are responsible for the uncontrolled growth of tumor cells. This may cause the tumor cells to
die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 2 dasatinib tablets
by mouth 2 times a day for the 4 weeks before surgery (in the morning and 12 hours later).
Dasatinib may be taken with or without food, but should be swallowed with at least 1 cup (8
ounces) of water. A light meal is not required, but may help you avoid getting a stomach ache
when you take your dose. Tablets must be swallowed whole and may not be broken. If vomiting
occurs within 30 minutes of swallowing the tablet(s), you can take another dose. If you miss
a dose of dasatinib, take it as soon as you remember on the same day. If you miss taking your
dose for 12 hours, take your regular dose the next scheduled day (do not take double your
regular dose to make up for the missed dose). You will be given a "pill diary" to write down
when you take the study drug. You will be shown how to fill it out and asked to bring the
diary with you to each clinic visit.

Study Visits:

On Days 21 and 28, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of vital signs and weight.

- You will also have a test to check the amount of oxygen in your blood.

- Blood (about 3-4 teaspoons) will be drawn for routine tests.

- You will have a performance status evaluation.

- You will have an ECG.

- Blood (about 1-2 teaspoons) will be drawn to check your how well your blood clots.

- You will have a PET scan to check the status of the disease. This PET scan will be
before your surgery, the study doctor will tell you when this will be performed.

Surgery:

After you have taken dasatinib for 28 days, you will have surgery to remove the tumor. You
will continue to take the dasatinib until midnight the night before the surgery. Depending on
the status of the disease, you will have either a pleurectomy or extrapleural pneumonectomy.
You will be given a separate consent for these procedures, which will describe the surgery
and any risks in detail.

Pleurectomy is the surgical procedure to remove the parietal pleura (the outermost lining
around the lungs).

An extrapleural pneumonectomy is a surgical procedure that removes portions of the lung, the
parietal pleura (the lining of the lung), the pericardium (the lining of the heart), and the
diaphragm.

During surgery, 5-6 core biopsies, if possible, will be taken from different areas of the
tumor for biomarker testing.

For the CT-guided core biopsy of the lung, a tissue sample is withdrawn from an organ or
suspected tumor mass using a very thin needle and a syringe. The needle is guided while being
viewed by the physician on a CT scan.

Length of Study:

After surgery, your doctor will decide the type of treatment you should receive for your
condition. If the disease responded well to the 4 weeks of dasatinib, you may be eligible to
continue taking dasatinib once a day starting 4-6 weeks after your surgery. The doctor may
also decide that you can take dasatinib once a day starting 4-6 weeks after receiving
radiation therapy. You may continue to take dasatinib as long as you are benefitting. You
will be taken off study if intolerable side effects occur or the disease gets worse.

Follow-up Visits:

If you continue to receive the study drug after surgery, you will have a physical exam and a
PET or CT scan every 8 weeks.

If you are taken off study for any reason, you will continue to be followed by the study team
to see how you are doing.

This is an investigational study. Dasatinib is an investigational agent and ongoing clinical
trials are using this drug in malignant mesothelioma. However, these studies have only
recently started, and there is no information so far that shows the drug is effective in
malignant mesothelioma. Dasatinib is FDA approved and commercially available for the
treatment of acute lymphoid and chronic myeloid leukemia.

However, its use in this research study is investigational.

Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.

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 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