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Impact of treatment with tetrathiomolybdate (TM) in dogs with appendicular osteosarcoma
To determine whether adding tetrathiomolybdate (TM) to standard chemotherapy treatment for OSA after limb amputation will help to prevent or slow the growth of tumor spread in the lungs of affected dogs.
The standard treatment for OSA is removal of the tumor (typically limb amputation) followed by chemotherapy to kill any tumor cells that may have already spread to other parts of the body. Unfortunately, in most cases not all the tumor cells are killed and most dogs with OSA will develop spread to the lungs (and sometimes other sites like other bones and liver/spleen) within 8-12 months of treatment. We now know that tumor spread (metastasis) requires the development of new blood vessels into it to provide oxygen and nutrients. Without those blood vessels, the tumor spread has difficulty growing. Based on this, several investigators have been developing new therapies directed at blocking the new blood vessel growth to help slow or prevent the growth of the spread. Research has shown that the element copper is a key factor in new blood vessel growth; blocking copper helps to slow the development of new blood vessels. One way to lower the whole body copper level is to prevent it from being absorbed in the stomach/intestine.
Tetrathiomolybdate (TM) is a drug given orally that works by binding copper in the diet, and after 1-3 months of administration, whole body copper concentrations are reduced to a level where the copper isn’t available to help new blood vessel growth. A pilot study of TM was performed in dogs with a variety of cancers and tumor shrinkage and slowing of tumor growth was seen in several dogs. Therefore it does appear that TM does have some anticancer activity in dogs, although it is not really known how this works in dogs with very small (microscopic) levels of tumor cells. The purpose of this clinical trial is to determine whether adding TM to standard chemotherapy treatment for OSA after limb amputation will help to prevent or slow the growth of tumor spread in the lungs of affected dogs.
• Histologically confirmed Osteosarcoma after limb amputation
• Have no evidence of metastatic disease (spread) on initial staging
• Owner consent/agreement to chemotherapy with carboplatin
• Owner availability for study duration of 12 months
• Carboplatin chemotherapy must be started within 14 days of amputation
• Evidence of metastatic disease at initial staging
• Pregnant or nursing
• Presence of any other disease that could affect outcome (i.e., heart disease, liver disease, kidney disease)
• Presence of any risk factor that would prevent the use of carboplatin chemotherapy
The dog must undergo various tests prior to study enrollment including complete blood count, chemistry panel, urinalysis, and chest x-ray. The chemotherapy (Carboplatin) is given every 3 weeks starting 14 days after amputation for 4 doses. At the time of study entry, dogs will be randomized to receive the TM or placebo, and owners will not know which drug the dogs are getting. The placebo is necessary as it is not clear that the TM will actually prevent the tumor spread from growing, so we need to compare the outcome with dogs that receive the standard therapy for disease. Dogs will be evaluated every 3 weeks for the first 4 months at the Ohio State Veterinary Medical Center, then once per month thereafter. Additionally, a complete blood count will need to be checked 10 days after the first 5 visits to OSU. This will be performed at OSU after first chemotherapy then you will be allowed to go to your local veterinarian. The first 4 visits are for the administration of the chemotherapy, and adjustment of TM dosing. Dogs enrolled in this clinical trial will have routine CBC and chemistry panel evaluations concordant with chemotherapy treatments and routine follow-up following completion of the chemotherapy protocol. Copper levels are measured at every visit and TM dose adjustments will be made based on the copper levels and the presence of any anemia. Any dogs that develop evidence of tumor spread while on study (i.e., nodules seen on a chest x-ray) will be unblinded (i.e., we will determine if they are receiving placebo or TM) and if they are receiving placebo, they will have an opportunity to start the TM.
Carboplatin will be provided at no cost
All visits after week 9 are completely covered by the study, including follow-up chest x-rays and bloodwork.
Owner is responsible for cost associated limb amputation, and the cost for the administration of chemotherapy. The estimated cost of chemotherapy is approximately total of $1300, including the initial visit, all chemo administration and bloodwork.
Please contact the Clinical Trials Office at the Veterinary Medical Center for more information about this study.