01426: Personalized Medicine for the Treatment of Canine Mast Cell Tumors

Grant Status: Closed

Grant Amount: $90,000
Douglas H Thamm, VMD; Colorado State University
January 1, 2011 - June 30, 2014

Sponsor(s): American Bullmastiff Association, Boston Terrier Club of America, Briard Club of America Health & Education Trust, Golden Retriever Foundation, Plum Creek Kennel Club of Colorado, Rhodesian Ridgeback Club of the United States, Saluki Health Research, Inc., Vizsla Club of America Welfare Foundation

Breed(s): -All Dogs
Research Program Area: Oncology
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Project Summary

While surgery remains the mainstay of treatment for canine mast cell tumors (MCT), surgery alone is not curative in some cases, and not possible in other cases. Medical therapy remains an important component of MCT therapy. New drugs that affect signaling through the KIT growth factor receptor are showing considerable promise for the treatment of canine MCT, and MCT with mutations in the KIT protein that make it constantly active may be more sensitive to KIT inhibitors. The drug combination vinblastine and prednisone has roughly the same effectiveness as KIT inhibition against canine MCT; however, the two treatments have not been compared head-to-head, and it is not clear whether vinblastine or KIT inhibitors are more appropriate for the treatment of MCT without KIT mutations. We recently developed a rapid test, which can be performed on fine-needle aspirates, to determine whether MCT possess KIT mutations or not. We investigated the predictive value of KIT mutation status using this rapid genotyping assay, as well as KIT staining on biopsy sections, in dogs with measurable MCT randomized to receive either vinblastine or the KIT inhibitor toceranib (Palladia?). Randomization utilized a novel adaptive statistical strategy that makes use of the KIT assay results.

87 evaluable dogs were enrolled in this study at 4 participating study sites. 59 dogs were randomized to receive toceranib and 28 dogs were randomized to receive vinblastine. 5 dogs. remain on-study. Statistical analysis will take place when these dogs have been removed from study.

The results of this study will clarify whether KIT mutation testing is a useful decision-making tool for the selection of the best possible medical therapy for dogs with MCT.

Publication(s)

Halsey, C. H. C., Thamm, D. H., Weishaar, K. M., Burton, J. H., Charles, J. B., Gustafson, D. L., … Ehrhart, E. J. (2017). Expression of Phosphorylated KIT in Canine Mast Cell Tumor. Veterinary Pathology, 54(3), 387–394. https://doi.org/10.1177/0300985816688943

Thamm, D. H., Weishaar, K. M., Charles, J. B., & Ehrhart, E. J. (2019, July 31). Phosphorylated KIT as a Predictor of Outcome in Canine Mast Cell Tumours Treated with Toceranib Phosphate or Vinblastine. https://doi.org/10.1111/vco.12525

Weishaar, K. M., Ehrhart, E. J., Avery, A. C., Charles, J. B., Elmslie, R. E., Vail, D. M., … Thamm, D. H. (2018). c-Kit Mutation and Localization Status as Response Predictors in Mast Cell Tumors in Dogs Treated with Prednisone and Toceranib or Vinblastine. Journal of Veterinary Internal Medicine, 32(1), 394–405. https://doi.org/10.1111/jvim.14889

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