A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma
OBJECTIVES:
Primary
- To determine the rate of progression-free survival (PFS) at 24 weeks (or 5.5 months) in
patients with malignant mesothelioma treated with dasatinib.
Secondary
- 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 at least every 2 months for 1
year, then every 4 months for 1 year, then every 6 months for 1 year.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
24 Week Progression Free Survival
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.
24 weeks
No
Arkadiusz Dudek, MD
Study Chair
Masonic Cancer Center, University of Minnesota
United States: Federal Government
CDR0000558362
NCT00509041
August 2007
December 2012
Name | Location |
---|---|
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
Memorial Hospital of South Bend | South Bend, Indiana 46601 |
CCOP - Greenville | Greenville, South Carolina 29615 |
CCOP - Northern Indiana CR Consortium | South Bend, Indiana 46601 |
Saint Joseph Regional Medical Center | South Bend, Indiana 46617 |
Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
Fletcher Allen Health Care - University Health Center Campus | Burlington, Vermont 05401 |
Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
Wayne Memorial Hospital, Incorporated | Goldsboro, North Carolina 27534 |
UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center | Washington, District of Columbia 20007 |
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center | Savannah, Georgia 31403-3089 |
Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
Methodist Estabrook Cancer Center | Omaha, Nebraska 68114-4199 |
Elkhart General Hospital | Elkhart, Indiana 46515 |
Howard Community Hospital | Kokomo, Indiana 46904 |
South Bend Clinic | South Bend, Indiana 46617 |
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center | Baltimore, Maryland 21237 |
Lakeland Regional Cancer Care Center - St. Joseph | St. Joseph, Michigan 49085 |
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | Columbus, Ohio 43210-1240 |
Fort Wayne Medical Oncology and Hematology | Fort Wayne, Indiana 46815 |
Center for Cancer Therapy at LaPorte Hospital and Health Services | La Porte, Indiana 46350 |
Cancer Institute of New Jersey at Cooper - Voorhees | Voorhees, New Jersey 08043 |
Iredell Memorial Hospital | Statesville, North Carolina 28677 |
Mountainview Medical | Berlin, Vermont 05602 |
Danville Regional Medical Center | Danville, Virginia 24541 |
Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
Missouri Baptist Cancer Center | St. Louis, Missouri 63131 |
Tunnell Cancer Center at Beebe Medical Center | Lewes, Delaware 19958 |
Union Hospital Cancer Program at Union Hospital | Elkton MD, Maryland 21921 |
Arch Medical Services, Incorporated at Center for Cancer Care and Research | Saint Louis, Missouri 63141 |
Kinston Medical Specialists | Kinston, North Carolina 28501 |