Articles and Resources
Verified by National Cancer Institute (NCI), January 2009
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.
Procedure: immunoenzyme technique
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
||Treatment, Open Label
||A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma
Primary Outcome Measures:
- Progression-free survival (PFS) at 24 weeks (or 5.5 months) [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Response rate
(complete and partial response) as measured by RECIST criteria [ Designated as safety issue: No ]
- Response duration [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Toxicity profile [ Designated as safety issue: Yes ]
- Correlation of expression levels of EphA2 and PDGFRβ with
response, PFS, and overall survival [ Designated as safety issue: No ]
- Correlation of
plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related
protein with response, PFS, and overall survival [ Designated as safety issue: No ]
- Correlation of a decrease in Src phosphorylation in PBMC with response,
PFS, and overall survival [ Designated as safety issue: No ]
- Correlation of a decrease
in the phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue with response [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Primary Completion Date:
||July 2008 (Final data collection date for primary outcome measure)
- 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 dasatinib.
- 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 mesothelioma.
- 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 dasatinib.
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 periodically.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Histologically confirmed malignant mesothelioma of any of the following subtypes:
Any site of origin of malignant mesothelioma allowed including, but not limited to, any of the following:
- 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
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
- Must 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 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
- No prior tyrosine kinase, signal transduction, or angiogenesis inhibitor therapy
At least 7 days since prior and no concurrent antithrombotic or anti-platelet agents, including any of the following:
At least 7 days since prior and no concurrent use of the following drugs:
- Ketoconazole (at doses > 200 mg/day)
- St. John's wort
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00509041
Cancer and Leukemia Group B
||Arkadiusz Dudek, MD
||Masonic Cancer Center, University of Minnesota
|Study ID Numbers:
|Study First Received:
||July 30, 2007
||January 15, 2009
Keywords provided by National Cancer Institute (NCI):
advanced malignant mesothelioma
recurrent malignant mesothelioma
Study placed in the following topic categories:
Neoplasms, Glandular and Epithelial
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on January 22, 2009
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors