A Phase II Study of Dasatinib (NSC 732517) in Previously-Treated Patients With Metastatic Colorectal Cancer
I. Determine the progression-free survival of patients with metastatic colorectal cancer who
have progressed on or following two prior chemotherapy regimens and are then treated with
I. Determine the objective response rates in patients treated with dasatinib. II. Determine
the overall survival of patients treated with dasatinib. III. Determine the toxicity in
patients treated with dasatinib.
I. Determine the incidence of somatic mutations in c-src, c-yes, fyn, lck, hck, lyn, yrk and
csk in archival primary and metastatic colorectal cancer tissues from these patients and to
correlate this with clinical outcome.
II. Determine the incidence of total c-src and phosphorylated c-src expression in archival
primary and metastatic colorectal cancer specimens from these patients, and to correlate
this with clinical outcome.
III. Evaluate the effect of dasatinib on serum VEGF levels.
OUTLINE: This is a multicenter study. Patients receive oral dasatinib twice daily on days
1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable
Blood is collected on days 1 (prior to the first dose of dasatinib) and 15 of course 1 for
measurement of VEGF pre-and post-dasatinib administration. Archived tumor tissue (tumor or
core biopsy; primary or metastatic lesion) is collected for identification of the incidence
of somatic mutations and polymorphisms by polymerase chain reaction and electrophoresis and
for measurement of total c-src and phosphorylated src expression by immunohistochemistry.
After completion of study treatment, patients are followed for at least 8 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Patients who are still alive and have not progressed will be censored as the data of the last negative examination. A Simon (1989), optimal, two-stage design will be employed.
From the start of treatment to the time of disease progression or death from any cause, assessed at 4 months after completion of treatment
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
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