Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer
|Recurrent Colon Cancer Recurrent Rectal Cancer Stage IV Colon Cancer Stage IV Rectal Cancer||Drug: dasatinib Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Dasatinib (NSC 732517) in Previously-Treated Patients With Metastatic Colorectal Cancer|
- Progression-free Survival Rate [ Time Frame: From the start of treatment to the time of disease progression or death from any cause, assessed at 4 months after completion of treatment (i.e., up to 12 months.) ]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 at the date of the last negative examination. A Simon (1989), optimal, two-stage design will be employed. The progression-free survival count will be the proportion of subjects who are alive and progression-free at 4 months.
- Response Rate (RR) (Complete or Partial Responders) [ Time Frame: Every 2 courses, assessed up to 8 weeks after completion of study treatment (i.e., up to 10 months) ]Response will be evaluated in this study using the new international criteria proposed by the RECIST Committee. The response rate is the proportion of subjects who experienced a complete or partial response.
- Incidence of Somatic Mutations [ Time Frame: 1 year ]Multivariable analysis of progression-free survival duration will be performed using the Cox (1972) regression model to evaluate the prognostic value of somatic mutations. For the mutational analysis endpoints, genetic mutations will also be correlated with drug activity via Fisher's exact test for comparisons of responders with non-responders and for comparison of patients progression-free and 4 months vs. those with early progression or death
- Association Between the Incidence of Total C-src and Phosphorylated C-src Expression and Response [ Time Frame: 4 months ]Examined by comparing expression in those who have an objective response versus those who do not and in those with and without disease progression at 4 months using Fisher's exact test.
- Change in Plasma Vascular Endothelial Growth Factor (VEGF) Levels Over 15 Days [ Time Frame: At baseline and day 15 ]Changes of VEGF will be correlated with response rates and 4-month progression-free survival utilizing the Wilcoxon rank-sum test.
|Study Start Date:||July 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tyrosine Kinase Inhibitor)
Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: laboratory biomarker analysis
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 dasatinib.
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 toxicity.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00504153
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|Principal Investigator:||Hedy Kindler||University of Chicago|