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

Phase 2
18 Years
Not Enrolling
Malignant Mesothelioma

Thank you

Trial Information

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



- To determine the rate of progression-free survival (PFS) at 24 weeks (or 5.5 months) in
patients with malignant mesothelioma treated with dasatinib.


- To determine the response rate (partial response [PR] and complete response [CR]) in
patients with malignant mesothelioma treated with dasatinib.

- To determine the response duration in patients with malignant mesothelioma treated with

- To describe the overall survival (OS) of patients with malignant mesothelioma treated
with dasatinib.

- To describe the toxicity profile of dasatinib in patients with malignant mesothelioma.

- To determine whether the amount of expression of EphA2 and PDGFRβ, as measured by
immunohistochemistry from tumor specimens, correlates with PFS in patients with
malignant mesothelioma.

- To determine whether plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and
soluble mesothelin-related protein correlate with PFS in patients with malignant

- To determine whether inhibition of Src phosphorylation in PBMC correlates with PFS.

- To assess inhibition of phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue by

OUTLINE: Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every
28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative
studies. Tumor tissue samples are analyzed for EphA2 and PDGFRβ expression by
immunohistochemistry. Tumor tissue samples may also be analyzed for phosphorylation of Src,
EphA2, and PDGFRβ by western blot. Blood samples are analyzed for concentration of VEGF and
PDGF by quantitative sandwich enzyme immunoassay technique; mesothelin-related protein level
by Mesomark® assay; CSF-1 level by ELISA assay; and phosphorylation of Src by phospho-Src
(pTyr418) human ELISA.

After completion of study treatment, patients are followed at least every 2 months for 1
year, then every 4 months for 1 year, then every 6 months for 1 year.

Inclusion Criteria


- 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

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

- No known brain metastases

- May be registered on CALGB-150707 companion study


- 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

- 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

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

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

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

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


- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

24 Week Progression Free Survival

Outcome Description:

Percentage of participants who were alive and progression free at 24 weeks. The 24 week progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Arkadiusz Dudek, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Federal Government

Study ID:




Start Date:

August 2007

Completion Date:

December 2012

Related Keywords:

  • Malignant Mesothelioma
  • advanced malignant mesothelioma
  • epithelial mesothelioma
  • recurrent malignant mesothelioma
  • sarcomatous mesothelioma
  • Mesothelioma



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