Palladia/Piroxicam/Cyclophosphamide Treatment for Dogs with Osteosarcoma

This Study is closed.

Purpose of Study

The purpose of this clinical trial is to evaluate the activity of piroxicam/cyclophosphamide versus Palladia/piroxicam/cyclophosphamide in dogs with OSA following amputation and standard chemotherapy and to compare this with a historical group of dogs treated with chemotherapy alone.

Background

Osteosarcoma (OSA) is the most common bone tumor in dogs, occurring in over 8,000 dogs each year in the United States and representing up to 85% of all bone tumors. Treatment involves amputation of the affected limb followed by chemotherapy. However, approximately 90% of dogs with OSA will die of spread of disease, usually to the lungs, within 2 years of amputation despite aggressive therapy. If significant improvements in survival time are to occur, new therapeutic approaches need to be explored. Palladia (toceranib phosphate), a new anti-cancer drug that works by blocking the signaling of several receptors, including VEGFR2, PDGFR and Kit. Inhibition of VEGFR2 and PDGFR works to slow down or block the growth of new blood vessels in tumors. Following FDA approval of in 2009, Palladia was used to treat dogs with a variety of cancers. To assess the potential impact of this drug on OSA, veterinary oncologists were solicited for cases in which Palladia was used to treat dogs with metastatic OSA. Biologic activity of Palladia in 22 dogs with metastatic OSA was reported as 45% for a median response duration of 23 weeks (range=7-47 weeks), significantly longer than the expected median survival time of 2 months for dogs with metastatic OSA treated with chemotherapy. Interestingly, most of the dogs treated with Palladia were also given low-dose cyclophosphamide and/or piroxicam. The use of low-dose cyclophosphamide and piroxicam is not new in veterinary medicine and at least 2 papers have been published providing preliminary evidence of activity of this drug combination in sarcomas in dogs. Piroxicam is a non-steroidal anti-inflammatory drug that is thought to help inhibit blood vessel growth by blocking an enzyme called COX-2. Cyclophosphamide is a chemotherapy agent that when given at a very low dose is thought to inhibit the growth and migration of new blood vessel cells. They are often given together in what is called a metronomic protocol/setting. The theory is that the combination of piroxicam and cyclophosphamide (at low doses) will help to inhibit the ability of tumors to grow new blood vessels, thus limiting their ability to grow and spread. There is now data from the human side suggesting that the combination of piroxicam/cyclophosphamide with an inhibitor or VEGFR2 may be better than the two drugs alone.

Inclusion criteria

To qualify for enrollment in this study, dogs must:

Have histologically confirmed diagnosis of OSA
The disease must be confined to the limb (OSA in areas other than the limbs cannot be included)
Weigh >10 kgs
Have undergone limb amputation <14 days prior to treatment initiation (first carboplatin dose)
Have not received chemotherapy or radiation prior to amputation
Have corticosteroids or NSAIDs discontinued at least 3 days before the first dose of carboplatin
Have no evidence of metastatic disease at the time of surgery

Study Design

Dogs with histologically confirmed OSA of the limbs undergoing limb amputation <14 days prior to treatment initiation will all be treated with 4 cycles of single-agent carboplatin. At the 4th treatment, all dogs will be re-staged with 3-view chest radiographs. Those dogs remaining free of metastatic disease will be randomized three weeks later into one of two groups to either receive Palladia, cyclophosphamide and piroxicam or only cyclophosphamide and piroxicam. 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. Chest radiographs will also be performed every 8 weeks. The total intended time for this study is 50 weeks since the date of surgery.

Client Compensation

The study will provide Palladia free of cost for duration of study and beyond
The study will provide a total of $1,130.00 divided between the visits to help alleviate the costs. That includes paying for the total cost of carboplatin and some of the recheck visits and tests.

Client Cost

Owner is responsible for the fees associated with the surgery and costs for each visit that exceed the amount covered by the study per visit.
Owner is responsible for any additional costs that arise from other medications, and the treatment of potential complications during the study.