Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma
Condition: Malignant Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms
Intervention: dasatinib
Intervention description: 50 mg PO bid
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced malignant mesothelioma; epithelial mesothelioma; recurrent malignant mesothelioma; sarcomatous mesothelioma

Summary:

      RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth.

      PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with
      previously treated malignant mesothelioma.
    

Eligibility 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