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Safety of Evaluation of Combination of Vinblastine and Toceranib (Palladia): A Phase I Dose-Finding Study
The purpose of this study is to determine the maximally tolerated dose of Palladia when used in combination with 4 weekly standard doses of vinblastine in dogs with mast cell tumors
Mast cell tumors (MCTs) are the second most common cancer in dogs. Vinblastine chemotherapy is the current standard of care for the treatment of high-risk or unresectable MCTs in dogs. Recently, the new veterinary tyrosine kinase inhibitor (TKI) toceranib (SU11654, Palladia®, Zoetis (Formally Pfizer)) was approved for the treatment of dogs with MCTs. As vinblastine and Palladia have different mechanisms of action, it is predicted that an increase in side effects will not occur if the drugs are given together. If such a combination was found to be safe, it could potentially increase the response rate and duration of response in dogs with MCTs compared to either drug alone. Therefore, the purpose of this clinical trial is to determine the maximally tolerated dose of Palladia when used in combination with a standard dose of vinblastine in dogs with MCTs.
To qualify for enrollment in this study, dogs must:
- Have a confirmed non-resectable MCTs or the owners choose not to have undergo surgical removal of the tumor
- Weigh >5 kgs
- No chemotherapy or radiation therapy within 3 weeks of enrollment
- No corticosteroid/nonsteroidal ant-inflammatory within 72hrs of enrollment.
Patients will receive 4 weekly doses of vinblastine in combination with escalating doses of Palladia, according to a prescribed dose increase scheme of Palladia. The dose of Palladia will begin at 2.5 mg/kg and increases will be made at 0.25 mg/kg with 3 dogs entered per dose level, up to a total dose of 3.25 mg/kg. When one dog in a dosing group experiences a dose limiting side effect (severe vomiting, diarrhea, low white blood cell count), the dosing group will be expanded to 6 dogs at that Palladia dose level. If no more dogs in the group experience dose limiting side effects, the dose of Palladia will be increased again. However, if the side effects occur in more than 1 dog in a dosing group, the dose will be decreased by 0.25 mg/kg which will then be considered the maximum tolerated dose. All 3 or 6 dogs at a particular dose level must be observed for the full 4 weekly treatments of vinblastine/Palladia before increasing the dose of Palladia to the next level to make sure that no dose limiting side effects are noted throughout the entire treatment period. All dogs on study will receive both diphenhydramine (Benadryl) and famotidine (Pepcid) to avoid side effects associated with histamine release from MCTs. At the conclusion of the 4 week study period, owners will be allowed to keep their dogs on Palladia therapy for a total of 6 months.
- Palladia will be provided at no cost during study and 6 months after end of study
- Study will cover fees related to recheck visits and scheduled bloodwork, as are supportive medications such as Benadryl and Pepcid
- Adverse events due to chemotherapy will be covered by the study
- Client is responsible for initial screening
Dr. Cheryl London
clinicaltrials [at] cvm [dot] osu [dot] edu