Kit mutation and localization status as response predictors in canine mast cell tumors treated with toceranib or vinblastine: A multi-center response-adaptive randomized trial

Purpose

 The goal of this study is to determine if canine mast cell tumors with kit mutation respond better to Palladia and whether screening for kit mutations play a role in treatment decision-making.

 Background

 Mast cell tumors (MCT) are the most common malignant skin tumors encountered in dogs. While surgery remains the mainstay of treatment for canine mast cell tumors it alone is not curative in some cases, and not possible in other cases. Medical therapy remains an important component of MCT therapy. New drugs such as Palladia (toceranib phosphate) 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 with Palladia 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 have recently developed a rapid test, which can be performed on fine-needle aspirates, to determine whether MCT possess KIT mutations or not. We intend to investigate 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 Palladia. Randomization will utilize a novel adaptive statistical strategy that makes use of the KIT assay results. 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.

 Inclusion criteria

 To qualify for enrollment in this study, dogs must have:

  • Histologically or cytologically confirmed cutaneous mast cell tumor of any grade;
  • Measurable disease of >1 cm
  • Age > 1 year;
  • A life expectancy of at least 12 weeks;
  • No evidence of other illness such as kidney, liver or heart disease;
  • At least 2 weeks apart from other investigational drug;
  • Not been treated previously with chemotherapy

 Study Design

 Dogs with MCT will undergo screening including complete blood count, chemistry panel, urinalysis and abdominal ultrasound to determine eligibility for the study.  A baseline tumor biopsy will then be obtained if my dog is found to be eligible.  Following biopsy, your dog will receive Benadryl, prilosec, and prednisone for at least 72 hours prior to treatment with either vinblastine or Palladia.  The determination of treatment protocol will be made by study personnel at Colorado State University.  If your dog has been assigned to receive vinblastine, the drug will be administered by intravenous injection once per week for 4 weeks, then every other week for another 4 treatments (total of 8 treatments).  If your dog has been assigned to receive Palladia, the drug will be administered orally on Monday, Wednesday, and Friday every week for a total of 3 months.  If progressive disease is noted during the planned treatments, then your dog will be removed from the study and other therapies will be offered.  Dogs in either treatment arm will be evaluated weekly for the first 4 weeks, then every other week for the next 8 weeks.  

  Client Compensation

 

  • The study will cover the cost of the initial biopsy and the majority of each visit (ranging from approximately $ 50-150)
  • Clients on the Palladia arm will receive the drug free of cost indefinitely

 Client Cost

 Owner is responsible for the initial office visit and screening tests, which  is estimated to cost $700

  • For each visit the owners are responsible for an estimated cost of $75-90/visit; dogs receiving Vinblastine will also be responsible for additional $20 (drug cost) and $58 (chemotherapy administration fee) at each treatment

 Contact Information

 Tamra Mathie, RVT- 614-247-8706