Analysis of Palladia Pharmacokinetics and Pharmacodynamics at Non-Label Dosing

Purpose of study

The goal of this study is to determine the pharmacokinetics (blood levels) of Palladia given to dogs with cancer at doses lower than that recommended on the label.

Background

Palladia (toceranib phosphate) is a new type of anti-cancer agent that works by blocking the function of several receptors on the surface of tumor cells, as well as on the surface of new blood vessels. These receptors include VEGFR2, PDGFR, and Kit, and Palladia prevents their ability to signal inside the cell. Based on previous work associated with Palladia, the maximum tolerated dose of this drug was established to be 3.25 mg/kg. However, preliminary evidence suggests that dogs receiving lower than this dose (range 2.5-3 mg/kg) still respond to therapy. It is therefore possible that dogs that receive these lower doses may have sufficient exposure to Palladia to induce an anti-tumor effect. The purpose of this study is to determine the blood levels of Palladia in dogs with cancer receiving doses lower than the established maximum tolerated dose of 3.25 mg/kg. This is important as evidence now indicates that lower doses of Palladia are associated with fewer side effects and more likely to result in continued administration of drug without the need for extensive drug holidays. We will also attempt to determine whether the blood level of Palladia correlates to levels of VEGF (a growth factor for blood vessels) and VEGFR2 (a receptor inhibited by Palladia) in the plasma.

Inclusion citeria

To qualify for enrollment in this study, dogs must:

  • Have a sarcoma, carcinoma, melanoma or other solid tumor (excluding histiocytic sarcoma and hemangiosarcoma) that has either failed standard therapy or for which the owner declines standard therapy
  • Have a life expectancy of approximately 90 days
  • Have completed any chemotherapy or radiation therapy at least 2 weeks prior to enrollment

Study Design

A total of 40 dogs will be enrolled in this study. All patients will have a baseline evaluation that includes complete blood count, chemistry panel, and urinalysis, as well as any appropriate imaging studies (ultrasound, x-rays, etc). Those dogs with underlying systemic illness (i.e., kidney disease, heart disease, liver disease) may not be eligible for the study if the clinician feels Palladia treatment will exacerbate these conditions. Eligible dogs will receive Palladia at a dose determined by the clinician in charge of the case (range 2.5-3 mg/kg every other day). Pharmacokinetic analysis will take place on days 1, 7, 14, 30, 60 and 90 of Palladia treatment with blood samples (2 ml) drawn at 6 and 8 hrs post drug administration. On day 30, extended pharmacokinetic analysis will occur including blood samples at 0, 1, 2, 6, 8, and 12 hours. Plasma will be saved for analysis of Palladia levels (to be performed by Zoetis (Formally Pfizer Animal Health)), plasma VEGF levels, and plasma VEGFR2 mRNA levels. At the completion of the study, dogs that respond to therapy will receive 6 months of free Palladia to treat their cancer.

Client Compensation

Palladia will be provided at no cost during, and 6 months after the completion of the study representing a savings of $1500-3000 to owners.

Client Cost

The owner is responsible for all other costs including office visits and bloodwork.

Contact Information

For more information on this study, please contact Tamra Mathie or Nicole Stingle at clinicaltrials [at] cvm [dot] osu [dot] edu.