02910: Open-Label, Phase-2 Clinical Trial of Chlorambucil and Toceranib for Canine Mast Cell Tumors
Grant Status: Closed
Abstract
Mast cell tumor (MCT) is the most common malignant canine skin tumor. Although all breeds are at risk, Boxers, Boston Terriers, Bulldogs, Labrador Retrievers, Beagles, Viszlas, Rhodesian Ridgebacks, Weimaraners, Shar-Peis and Schnauzers are predisposed. While surgery remains the main treatment for most MCT, a subset have a high potential for eventual recurrence and metastasis and require systemic medical therapy following surgery in an attempt to delay or prevent eventual metastasis. Furthermore, many dogs may present with disease that is not amenable to resection owing to size, location, or multifocal or disseminated disease. Medical therapy for these patients remains suboptimal. Both low dose continuous (metronomic) chlorambucil (MC) and toceranib (TOC, Palladia) have some reported activity against MCT, and the combination is sometimes utilized clinically. However, (1) there have been, to date, no studies demonstrating that the empirically determined dose of MC exerts biologic effects; (2) the combination of MC and TOC has not been systematically evaluated for safety or efficacy in any tumor type. Investigators will address these critical knowledge gaps with a clinical trial to characterize the antitumor effects and adverse effect profile associated with chlorambucil/TOC in dogs with measurable MCT and quantify changes in circulating Treg and MDSC following MC and subsequent TOC treatment in the patient population. Lastly, they aim to describe alterations in previously identified biomarkers of TOC exposure and interrogate novel MC/TOC exposure biomarkers through gene-expression profiling of peripheral blood mononuclear cells. They hypothesize that a combination of MC and TOC will be well tolerated and will cooperatively reduce circulating regulatory T cells (Treg) +/- myeloid-derived suppressor cells (MDSC) in dogs with MCT, with the potential to translate into improved tumor control.
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Publication(s)
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