College of Veterinary Medicine

Purpose of Study

The purpose of this study is to define the biologic activity of Palladia alone or in combination with radiation therapy for the treatment of nasal carcinoma.

Background

Nasal tumors comprise approximately 1% of canine tumors and carcinomas are diagnosed in 60-70% of cases.  Radiation therapy is the treatment of choice and is the only modality which has resulted in improvement of survival times. Reported survival times average 10-14 months following radiation therapy. The maximum tumor response is noted at approximately 3 months after completion of therapy and long term control rarely occurs. Both VEGF and VEGFR have been documented to be expressed in canine nasal carcinomas suggesting that inhibiting the VEGFR signaling axis may be therapeutically useful. This is supported by recent data presented at the 2010 Annual Veterinary Cancer Society Conference demonstrating clinical benefit in dogs with recurrent nasal carcinomas treated with the small molecule receptor tyrosine kinase inhibitor Palladia that inhibits signaling of VEGFR family members. One of the dogs experienced a complete response to therapy after failing radiation, suggesting that Palladia may have single agent activity against this disease. While there are no published data demonstrating the use of Palladia in combination with radiation, evidence from mouse models  indicates that VEGFR inhibitors can act synergistically with radiation therapy without an increase in toxicity. Indeed, data presented at the VCS meeting demonstrated no enhanced toxicity when radiation was combined with Palladia for the treatment of mast cell tumors in dogs.

Inclusion criteria

To qualify for enrollment in this study, dogs must:

• Have histologically confirmed diagnosis of nasal carcinoma
• Have a tumor that does not extend through the cribiform plate into the brain parenchyma (evaluated on computerized tomography scan)
• Have no evidence of metastatic disease at the time of enrollment
• Have no other serious health problems that are incompatible with the study (as renal, cardiac or hepatic insufficiency)
• Have a life expectancy greater than 6 weeks

Study Design

Dogs with confirmed diagnosis of nasal carcinoma will receive Palladia every other day and depending on owner preference, will also receive radiation therapy (10 daily treatments over two weeks). Recheck exams will be performed at 1, 2, and 4 weeks after initiating Palladia, and then every 4 weeks thereafter for a total of 1 year.  For those dogs that receive radiation therapy, a CT scan will be repeated by the Radiation Oncology Service at 3, 6, and 12 months following radiation treatment. For those dogs that do not receive radiation therapy, a CT scan will be performed at 3 months following therapy only.

Client Compensation

The study will cover most of the recheck visits and tests (bloodwork, CT scans) performed after the Palladia therapy is initiated representing a savings of approximately $3100.

Client Cost

Owners are responsible for the costs of the radiation therapy (approximately $2200 for the entire 2 week protocol). The majority of the costs for recheck visits after initiation of Palladia therapy are covered by the clinical trial amounting to a savings of approximately $3100. Owners are responsible for a small fraction of the costs for these recheck visits; this amounts to approximately $700 over the course of the 1 year period ($60/month). Owners are responsible for any additional costs that arise from other medications, and the treatment of potential complications during the study.

Contact Information

Please contact the Clinical Trials Office (clinicaltrials [at] cvm [dot] osu [dot] edu) at the Veterinary Medical Center for more information about this study.