Clinical, molecular, and immune characterization of naturally occurring osteosarcoma in dogs (COTC034)

The purpose of this study is to better understand the biology of primary bone cancer of the leg (appendicular osteosarcoma, OS) in dogs. This is a common cancer that occurs in dogs and it is often closely compared to OS in humans (primarily adolescents). The standard approach to treating dogs with OS is amputation of the affected leg, followed by chemotherapy. In this case, half the dogs have spread of OS to the lungs within 6 months despite amputation and chemotherapy, and half have died of disease by 10-11 months. Only a small proportion of dogs are long term survivors, living beyond 2 years. There is an increasing effort to study new treatments in pet dogs with OS to develop better, more effective therapies for both people and pets. This is known as comparative and translational canine cancer research. However, a big challenge for this effort is that we still don’t completely understand the natural biology of OS in dogs...that is, we don’t; know what happens when dogs with OS undergo amputation alone (i.e., no chemotherapy). In this study, we will follow dogs that get amputation alone to see if and when they develop tumor spread. As part of this effort, we will collect samples of the tumor after amputation, and blood samples periodically from your dog to study your dog’s immune system.

Your dog must have a diagnosis of OS (generally obtained by a needle aspiration) and no evidence of spread of OS to the lungs based on x-rays of the chest. Your dog must also have no obvious evidence of any other underlying disease like heart, liver or kidney disease and must have normal blood counts.

Inclusion Criteria

• Histologically or cytologically (consistent with a mesenchymal neoplasm)confirmed appendicular osteosarcoma, which includes all long bones of the limbs (radius, humerus, ulna, femur, and tibia), but excludes metatarsus, metacarpus, carpal and tarsal bones, and digits. Patients for which sampling is not clinically indicated, or is non-diagnostic, can be enrolled based on radiographic suspicion of OSA.
• In the opinion of the investigator, be considered a good candidate for amputation
• Dogs must weigh  25 kg prior to surgery
• Measurable disease that is amenable to surgical removal via amputation (No evidence of metastasis based upon physical exam, thoracic radiographs, and abdominal ultrasound).
• Favorable performance status: Grade 0 or 1 (modified ECOG criteria)
• ONLY newly diagnosed dogs are eligible with no prior therapy (conventional, metronomic, immunotherapeutic or experimental chemotherapy, ionizing radiation, bisphosphonates) for osteosarcoma
• Dogs receiving analgesics including NSAIDs, gabapentin, tramadol, amantadine, or similar will be eligible for study inclusion
• Liver ALT is equal to or less than 2.5x normal reference range IF patient has been managed with NSAID therapy at the time of presentation. If no current usage of NSAIDs, eligibility will remain the defined 1.5x normal reference range.
• Informed owner consent for trial
• IACUC approval at respective enrollment institution
• Dogs must undergo a full post-mortem examination (necropsy) if they die while in study

Exclusion Criteria

• Concurrent medications deemed incongruent with this study including apoquel, corticosteroids, or other immunosuppressive therapies.
• Significant co-morbid illness, which includes but is not limited to renal or hepatic failure, history of congestive heart failure or clinical coagulopathy.
• HCT < 25%, platelets < 100,000 cells/ul (in the absence of significant platelet clumping as perceived by the trials clinician)
• Any hematologic/biochemical (excluding ALT or ALP-detailed above and below) abnormalities > grade 1 (VCOG-CTCAE).
• Total ALP elevation higher than 5-fold increased upper reference range, in the concurrent absence of significant ALT elevations (Grade I (1.5xULN) or less)

Client Benefits

There are no direct benefits to your dog for participating in this study other than the fact that the amputation is provided at no cost, as is the follow up. We are not providing any interventional treatments for the OS other than removal of the primary tumor (i.e., amputation of the affected leg).

The study covers all costs associated with amputation and follow up visits to monitor for evidence of tumor spread The study would cover any costs directly related to complications related to the blood draw in the unlikely event something should occur. However, the study will not cover the costs associated with care for conditions unrelated to this study (i.e., bladder infection).

Sample or Data Requirements