Veterinary Speciality: Oncology
The purpose of this study is to evaluate the use of a new immune therapy in dogs with osteosarcoma, a malignant tumor that affects the long bones in dogs. The standard treatment for dogs with osteosarcoma is amputation of the affected leg followed by generally 4 treatments with a chemotherapy drug called carboplatin. Unfortunately, 25-30% of affected dogs will develop spread of the osteosarcoma to the lungs before chemotherapy treatment is completed, and 50% of all dogs will have spread within 6-8 months following amputation. Only 15% of dogs will live for two years after amputation. Therefore, new therapies for this cancer are desperately needed. There is increasing evidence that the immune system can recognize and kill osteosarcoma cells. A few recent studies in dogs with osteosarcoma using different ways to stimulate the immune systen have been promising. However, most of them are not used until after the amputation/surgical site has healed or until after the chemotherapy treatments have been finished. This gives the remaining tumor cells a chance to continue growing and find ways to evade the immune system. The purpose of this study is to use a new method to stimulate the immune system prior to amputation and then immediately after amputation wtihout the need for chemotherapy. This is the time when remaining tumor cells are most vulnerable to attack by the immune system and when it is easiest to prevent them from taking up residence in the lungs and other organs. In the current study, a combination of drugs that are given orally will be used to stimulate the immune system. This combination of three drugs includes: 1) Toceranib (Palladia), a drug that is approved to treat cancer in dogs. Toceranib has been shown to decrease two types of immune cells that actively block activation of other immune cells against the cancer. 2) Losartan, a blood pressure medication that has been shown block also help regulate the flow of immune cells into the tumor. And 3) Ladarixin, a drug that blocks a key receptor (IL-8 receptor) immune cells use to help block the action of other immune cells. These three drugs work together to target key parts of the immune system and retool their functions so that they can now kill the tumor cells. We have seen evidence that these three drugs can work in dogs with osteosarcoma that have already failed chemotherapy treatment with carboplatin after amputation. Based on these findings, we believe that the drug combination will work better when the number of cancer cells is much lower and before they have been exposed to chemotherapy and given a chance to become resistant to treatment.
Eligible dogs (all breeds) must meet all of the following criteria:
Dogs with any of the following will not be eligible for the study:
The study will cover the office visit, x-rays, and blood work prior to amputation to determine eligibility; the study will not cover the needle aspiration required for diagnosis (approximately $350). The study will cover $1500 of the approximate $3000-3500 total cost for amputation of the affected leg. The study will also cover all of the costs associated with drug administration, blood work, and x-rays for up to one year (12 months) after amputation up to a total of $5500 (including the $1500 for amputation). The study will not cover costs associated with complications secondary to amputation (i.e., infection), but will cover all costs associated with side effects from the drug therapy. The study will not cover costs associated with conditions unrelated to the osteosarcoma treatment (skin infection, ear infection, etc.).
Your dog will need to have a diagnosis of osteosarcoma based on either a biopsy of the tumor or a needle aspiration of the tumor. Blood work and chest x-rays will also need to be performed to make sure that there is no obvious evidence of tumor spread in the lungs and that the liver, kidneys and other body systems are functioning normally. Your dog also needs to be comfortable enough to delay amputation for 10-14 days so that that the oral drugs can be started before the tumor is removed (i.e., your dog cannot have a fracture of the bone or be unable to bear any weight at all/be in substantial pain). Once enrolled, your dog will receive the combination of toceranib/losartan/ladarixin at home. Approximately 72 hours prior to the amputation, the toceranib will be stopped, although the losartan and ladarixin will continue to be given. At 1 week post amputation, the toceranib will be re-started. Your dog will be evaluated 2 weeks following the toceranib re-start, then monthly for the first year. The toceranib/losartan/ladarixin will be continued for a total of 6 months, after which the drug regimen will be stopped. At 12 months post amputation, the recheck exams will be changed to every 2 months for another 12 months. At each study visit beginning at week 5, chest x-rays will be taken and blood will be drawn to evaluate cell counts and organ function, as well as for assays to monitor the immune response.
For questions regarding the clinical trial please email the clinical trials technician, Diane Welsh at: email@example.com
If you believe that your pet may be eligible for this study, please complete our prescreening questionnaire for owners.