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Clinical Trial
. 2012 Jun;30(3):1211-5.
doi: 10.1007/s10637-011-9681-x. Epub 2011 May 7.

Dasatinib in previously treated metastatic colorectal cancer: a phase II trial of the University of Chicago Phase II Consortium

Manish R Sharma  1 , Kristen Wroblewski, Blase N Polite, James A Knost, James A Wallace, Sanjiv Modi, Bethany G Sleckman, David Taber, Everett E Vokes, Walter M Stadler, Hedy L Kindler
Affiliations
Clinical Trial

Dasatinib in previously treated metastatic colorectal cancer: a phase II trial of the University of Chicago Phase II Consortium

Manish R Sharma et al. Invest New Drugs. 2012 Jun.

Abstract

Background: Treatment options for metastatic colorectal cancer (CRC) are limited after a fluoropyrimidine, oxaliplatin and irinotecan; novel agents need to be explored in this setting. Dasatinib, an oral inhibitor of Src family kinases, inhibits proliferation in CRC cell lines and has antitumor activity in CRC xenograft models.

Patients and methods: We conducted a multi-center phase II trial of dasatinib in unresectable, previously-treated metastatic CRC patients. No more than 2 prior chemotherapy regimens were permitted, which must have contained a fluoropyrimidine, oxaliplatin and irinotecan. The primary endpoint was progression-free survival (PFS) at 4 months. The Simon two-stage design required that at least 5 of the first 19 patients be progression-free at 4 months to expand to a second stage.

Results: Nineteen patients enrolled at 9 centers. The study was terminated after the first stage due to lack of efficacy. There were no objective responses; 1 patient (5%) had stable disease for 7.3 months. The PFS rate at 4 months was 5.3% (90% CI: 0.3, 22.6). Median PFS was 1.6 months (90% CI: 1.4, 1.8). Median overall survival was 5.1 months (90% CI: 2.4, 6.3). Grade 3/4 toxicities included fatigue in 16% of patients, and anemia, anorexia, nausea/vomiting and dyspnea in 11%.

Conclusion: Dasatinib is inactive as a single agent in previously treated metastatic CRC patients.

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Figures

Fig. 1
Fig. 1
Kaplan-Meier estimate of progression-free survival (PFS)
Fig. 2
Fig. 2
Kaplan-Meier estimate of overall survival
See this image and copyright information in PMC

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