Open-Label, Phase-2 Clinical Trial of Chlorambucil and Toceranib for Canine Mast Cell Tumors

MCT is the most common malignant cutaneous tumor in the dog. While aggressive surgery remains the mainstay of treatment for most canine MCT, a subset have a high potential for eventual recurrence and metastasis. In these patients, systemic medical therapy is usually recommended 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) have some reported activity against MCT, and the combination is sometimes utilized clinically. However; (1) There have been, to date, no studies demonstrated 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. We intend to address these knowledge gaps with this trial.

Participation Requirements:

Inclusion criteria: Dogs with histologically or cytologically confirmed, measurable MCT of any stage and grade, where surgical excision is not feasible or has been declined will be treated. All dogs will undergo complete clinical staging, to include complete blood count, serum biochemistry profile, aspiration of the regional lymph node, and abdominal ultrasound +/- needle aspiration cytology of abnormal structures. Dogs will be eligible if they have adequate hematologic and biochemical parameters to safely undergo therapy, absence of severe concurrent disease, and a modified ECOG performance status of 0 or 1. (0, normal activity; 1, restricted activity [decreased activity from pre-disease status]; 2, compromised [ambulatory only for vital activities, consistently defecates and urinates in acceptable areas]; 3, disabled [dog needs to be force-fed, is unable to confine urination and defecation to acceptable areas], and; 4, dead).

Specific exclusion criteria are:

• Serum transaminases exceeding 3x ULN
• Serum bilirubin exceeding the reference range
• Serum creatinine exceeding 1.5x ULN
• Neutrophils < 2,000/mL, platelets < 75,000/mL, hematocrit < 25%
• Dogs with a concurrent medical disorder likely to result in death or euthanasia within three (3) months or a condition which may be disruptive to the intent and objectives of the study
• Anticipated poor owner compliance
• Dogs that are pregnant or likely to become pregnant
• Dogs that are participating in another clinical trial
• Dogs that are scheduled for any elective procedure or medical treatment during the study period.
• Dogs that are unavailable for the duration of the trial or that are felt unsuitable by the Principal Investigator for any other reason.

Prior nonsurgical treatment will not be permitted, nor will concurrent treatment be allowed.

Owners Responsibilities:

Owners are responsible for bringing their pets to CSU for each appointment for the clinical trial (every 2 weeks for the first 6 weeks and then every 6 weeks). Owners must also be comfortable administering oral medications to their dogs at home.

Dogs must come to the CSU VTH for all appointments for the study. Dogs must live in a location that will allow for repeated visits to the VTH. Samples for this study cannot be sent from other clinics or owners.