Optimizing integration of veterinary clinical research findings with human health systems to improve strategies for early detection and interventions involving splenic hemangiosarcoma

Hemangiosarcoma (HSA) is a cancer of the cells lining the blood vessels that is very aggressive; it accounts for 5-7% of all cancers in dogs resulting in approximately 25-50,000 new cases per year. The standard treatment of choice is surgical removal followed by chemotherapy administration with a drug called doxorubicin (DOX). Unfortunately, despite surgery and DOX chemotherapy, nearly all dogs die within 6-8 months post-diagnosis. This cancer also represents a significant challenge because it is very hard to know when the disease has begun to come back as it typically spreads in the abdomen and chest (i.e. not the outside of the body).

It has been known for a long time that tumors release a small portion of their contents, particularly their DNA, into the bloodstream. This has resulted in a substantial effort to use the circulating DNA (ctDNA) to develop tools for early detection of cancer, identification of cancer recurrence, and monitoring of response to therapy. This is now known as a liquid biopsy (also blood biopsy; a blood sample essentially serves as a replacement for a tumor biopsy). We have recently developed an assay that can test for genetic mutations in HSA using the ctDNA. This test permits us to determine what drugs beyond standard chemotherapy could be useful in treating the cancer. Specifically, there are several drugs, called small molecule inhibitors, that work by blocking key proteins in tumor cells that help support their survival. These inhibitors are all given orally and have aleady been approved for use in humans. By combining chemotherapy with the small molecule inhibitors that are meant to target specific mutations/proteins in your dog’s tumor, we are hoping that we can improve outcomes for this aggressive cancer.

The potential benefit from the study is that the combination of chemotherapy plus oral small molecule inhibitors will improve outcomes over chemotherapy alone. Also, it is possible the frequent liquid biopsy checks to be done with the study may help in detecting recurrence of the HSA early. By intervening with new therapies prior to obvious evidence of cancer relapse, it is possible that new treatments will be more likely to control the cancer (i.e., when there are fewer cancer cells present).

Inclusion Criteria

Exclusion Criteria

Client Benefits

Sample or Data Requirements

At approximately 2 weeks post surgery (Week 2 of the study), your dog will receive the first treatment with DOX. Your dog will return on Week 3 for a recheck exam, bloodwork and to start the oral medications. Your dog will then return on Week 5 for a whole body CT scan under sedation to evaluate your dog for any evidence of tumor spread. If negative, then the second dose of chemotherapy will be given. Additional chemotherapy treatments will be given at Weeks 8 and 11. Another whole body CT scan will be performed at Week 14 prior to the final chemotherapy treatment. The next study visit will occur 4 weeks later, with the following study visits occurring every 2 months. The CT scan will be repeated on Weeks 22, 30, 38, 46 and 54. The study ends at the time of cancer spread. If your dog has evidence of tumor relapse based on the liquid biopsy test or a CT scan, then we will switch your dog to a new chemotherapy drug called vinblastine which is also used to treat HSA. We will next adjust the oral small molecule inhibitor combination based on the new genetic profile that we get from the liquid biopsy. The treatment cycle will be reset to Week 2 of the protocol, and we will move through the 5 chemotherapy treatments again. Each blood draw during the study will be for approximately 35 ml which equates to 2.5 tablespoons.

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