A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant mesothelioma of any of the following subtypes:

- Epithelial

- Sarcomatoid

- Mixed

- Any site of origin of malignant mesothelioma allowed including, but not limited to,
any of the following:

- Pleura

- Peritoneum

- Pericardium

- Tunica vaginalis

- Pathology blocks or slides from a core surgical biopsy must be available

- Not amenable to curative surgery

- Measurable disease, defined as lesions that can be accurately measured in at least
one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional
techniques (CT scan , MRI, or x-ray) or as ≥ 10 mm with spiral CT scan

- Patients with pleural rind only disease must have at least one level with one
rind measurement ≥ 1.5 cm

- Lesions that are considered nonmeasurable include the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Prior treatment with one and only one systemic chemotherapy regimen, which must have
included pemetrexed disodium required

- Treatment may have been with pemetrexed disodium alone or in combination with
any other agent

- No symptomatic pleural effusions, unless the patient undergoes a therapeutic
thoracentesis

- Patients with pleural effusions who have had a pleurodesis are eligible

- No known brain metastases

- May be registered on CALGB-150707 companion study

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Granulocytes ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Total bilirubin ≤ 2 x upper limit of normal (ULN)

- AST (SGOT) ≤ 2.5 x ULN

- Creatinine clearance ≥ 60 mL/min

- INR < 1.5

- PTT < 40 seconds

- QTc < 450 msec

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No significant cardiac disease, including any of the following:

- New York Heart Association (NYHA) class III-IV congestive heart failure (CHF)

- Unstable angina

- Myocardial infarction or ventricular tachyarrhythmia within 6 months of study
entry

- Ejection fraction less than institutional normal (in patients with a history of
CHF or currently with NYHA class I or II CHF)

- Prolonged QTc > 450 msec (Fridericia correction)

- Major conduction abnormality, unless a cardiac pacemaker is present

- Hypokalemia or hypomagnesemia that cannot be corrected

- No history of significant bleeding disorder unrelated to cancer, including any of the
following:

- Congenital bleeding disorder (e.g., von Willebrand disease)

- Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII
antibodies)

- Ongoing or recent (≤ 3 months) significant GI bleeding or hemoptysis

- No requirement for supplemental oxygen (i.e., pulse oximetry < 89% at rest)

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since prior pemetrexed disodium-containing chemotherapy

- At least 4 weeks since prior major surgery

- At least 4 weeks since prior radiation therapy

- Measurable disease must be outside the radiation port

- Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed

- Intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy

- At least 7 days since prior and no concurrent antithrombotic or anti-platelet agents,
including any of the following:

- Aspirin or aspirin-containing combinations

- Clopidogrel

- Dipyridamole

- Tirofiban

- Epoprostenol

- Eptifibatide

- Cilostazol

- Abciximab

- Ticlopidine

- Warfarin

- Low-dose warfarin for prophylaxis to prevent catheter thrombosis allowed

- Heparin or low molecular weight heparin

- Heparin for IV line flush allowed

- At least 7 days since prior and no concurrent use of the following drugs:

- Itraconazole

- Ketoconazole (at doses > 200 mg/day)

- Miconazole

- Voriconazole

- Telithromycin

- Primidone

- Rifabutin

- Rifampin

- St. John's wort

- Carbamazepine

- Oxcarbazepine

- Rifapentine

- Phenobarbital

- Phenytoin

- Quinidine

- Procainamide

- Disopyramide

- Amiodarone

- Sotalol

- Ibutilide

- Dofetilide

- Erythromycin

- Clarithromycin

- Chlorpromazine

- Haloperidol

- Mesoridazine

- Thioridazine

- Pimozide

- Bepridil

- Droperidol

- Halofantrine

- Levomethadyl

- Sparfloxacin

- No concurrent H2 blockers or proton pump inhibitors

- No bisphosphonate therapy during the first 8 weeks of study treatment

- No concurrent hormones or other chemotherapeutic agents except for steroids
administered for dasatinib-related pleural effusion or hormones administered for
non-disease-related conditions (e.g., insulin for diabetes)

- No concurrent palliative radiation therapy