Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-Adenoid Cystic Malignant Salivary Tumors
I. Determine the objective response rate (complete and partial response) in patients with
recurrent or metastatic c-KIT-expressing adenoid cystic carcinoma (ACC) of the salivary
gland treated with dasatinib.
II. Determine the progression-free survival of these patients.
I. Determine the duration of response in patients with non-ACC or c-KIT-expressing ACC of
the salivary gland.
II. Determine the stable disease rate and duration of stable disease in these patients.
III. Determine the median survival of these patients. IV. Determine the overall survival of
these patients. V. Determine the safety and tolerability of dasatinib in these patients. VI.
Determine the progression-free survival of patients with non-ACC of the salivary gland.
I. Correlate biomarkers that relate to Src signal transduction with clinical response to
dasatinib in patients with non-ACC or c-KIT-expressing ACC of the salivary gland.
II. Determine if activating mutations in PDGFA and KIT are associated with response in
patients with c-KIT-expressing ACC of the salivary gland.
OUTLINE: This is a multicenter study.
Patients are assigned to 1 of 2 cohorts according to histologic subtype (adenoid cystic
carcinoma [ACC] vs non-ACC).
Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.
Blood and tumor tissue samples are collected at baseline for correlative laboratory
biomarker and pharmacogenomic studies. Samples are analyzed for total c-Src and
phosphorylated Src expression by IHC; polymorphisms and gene rearrangements/activating
mutations in PDGFA (within exons 18 and 12) and KIT (within exons 9, 11, 13, and 27) by PCR;
and additional biomarkers associated with Src signal transduction and/or dasatinib response
(e.g., phospho-KIT, phospho-PDGFR, EPHA2, VEGF, Stat3, Bcl-x, survivin, cyclin D1, and
p27_Kip) by IHC.
After completion of study therapy, patients are followed at 4 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Up to 4 weeks
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Medical University of South Carolina||Charleston, South Carolina 29425-0721|
|Loyola University Medical Center||Maywood, Illinois 60153|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|Mount Sinai Medical Center||New York, New York 10029|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Central Illinois Hematology Oncology Center||Springfield, Illinois 62701|
|City of Hope Medical Center||Duarte, California 91010|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Tower Cancer Research Foundation||Beverly Hills, California 90211|
|Emory University||Atlanta, Georgia 30322|
|USC Norris Comprehensive Cancer Center||Los Angeles, California 90089|
|U.T.M.D. Anderson Cancer Center||Houston, Texas 77030|
|Decatur Memorial Hospital||Decatur, Illinois 62526|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|M D Anderson Cancer Center||Houston, Texas 77030|
|Northern Indiana Cancer Research Consortium||South Bend, Indiana|
|Evanston CCOP-NorthShore University HealthSystem||Evanston, Illinois 60201|
|Joliet Oncology-Hematology Associates Limited||Joliet, Illinois 60435|
|Illinois CancerCare-Peoria||Peoria, Illinois 61615|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Saint John's Mercy Medical Center||Saint Louis, Missouri 63141|
|The North Division of Montefiore Medical Center||Bronx, New York 10466|
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|
|Oncology Care Associates PLLC||St. Joseph, Michigan 49085|
|University of Michigan University Hospital||Ann Arbor, Michigan 48109|
|Mercy UC Davis Cancer Center||Merced, California 95340|
|Virginia Commonwealth University/Massey Cancer Center||Richmond, Virginia 23298|