College of Veterinary Medicine

Purpose

The goal of this study is to determine the anti-tumor activity of Palladia against canine hemangiosarcoma.

Background

Hemangiosarcoma (HSA) is a common cancer in dogs that arises from vascular endothelium (blood vessels). HSA have a very aggressive biologic behavior, and in most cases, rapid and widespread metastasis. Death due to disease is seen in 90% of patients within 1 year when treated with doxorubicin based chemotherapy. It has been demonstrated that the majority of canine HSA express the receptor tyrosine kinases KIT and VEGFR2, both of which are targets of the veterinary tyrosine kinase inhibitor (TKI) toceranib (SU11654, Palladia^®, Zoetis (Formally Pfizer)). Furthermore, it has been demonstrated that both VEGFR2 and KIT signaling can be blocked in HSA tumor cells, and that blocking these pathways in mouse models of canine HSA can slow tumor growth. This study is an open-label, single-arm, phase-II, multicenter clinical trial, and is first evaluation of KIT/VEGFR2 inhibitors as therapy for dogs with HSA.

Inclusion Criteria

To qualify for enrollment in this study, dogs must:

• Have histologically confirmed, stage I or II (i.e., no evidence of metastasis at the time of diagnosis) splenic HSA
• Weigh >5 kgs
• Have undergone splenectomy <21 days prior to treatment initiation
• Have received 5 doses of single-agent doxorubicin following spleen removal (one treatment every 2 weeks)

Study Design

Dogs with histologically confirmed, stage I or II, splenic HSA undergoing spleen removal <21 days prior to treatment initiation will all be treated with 5 cycles of single-agent doxorubicin. Two weeks following the 5^th treatment, all dogs will be re-staged with abdominal ultrasound and 3-view chest radiographs. Those dogs remaining free of metastatic disease will receive Palladia every other day. They will be rechecked at week 1, week 2, and week 4 following treatment initiation and then every 4 weeks thereafter. A complete blood count will be performed at every visit. A serum biochemistry profile and urinalysis will be performed every 8 weeks thereafter. Complete re-staging, consisting of chest radiographs and abdominal ultrasound, will be performed every 8 weeks following Palladia initiation for a total of 32 weeks of follow-up following initiation of Palladia therapy.

Client Compensation

• Initial screening including chest x-rays, lab work and abdominal ultrasound are covered by the study
• The study will provide Palladia free of cost for duration of study and beyond
• All fees related to recheck visits, scheduled bloodwork and imaging (chest x-rays, ultrasound) are covered by the study

Client Cost

• Owner is responsible for the fees associated with the Splenectomy and 5 doxorubicin treatments
• Owner is responsible for $20/visit and any additional costs that arise from other medications, and the treatment of potential complications during the study

Contact Information

Dr. Cheryl London
clinicaltrials [at] cvm [dot] osu [dot] edu