Research update from Dr. Modiano for Shine-On Hemangiosarcoma project looking into treatment of this disease.
During the 30 months that the project has been active, we have made substantial progress toward our objectives, and from the experience we have gained, we have made some adjustments to the experimental set-up. The project goals have not been modified. Specifically:
1. As of August 20, 2018, we had tested the parameters of the detection test on 74 dogs that had diagnoses of hemangiosarcoma, non-malignant spleen masses, other tumors, or no apparent illness.
2. We updated and refined the criteria and the algorithms to identify hemangiosarcoma cells in circulation, and to use this as a test for early detection of hemangiosarcoma for dogs at risk. We have observed cells that have the predicted “hemangiosarcoma progenitor” markers in dogs with other conditions (other tumors such as melanoma, osteosarcoma, and possibly dogs with benign splenic hematomas). So, we have included additional markers to increase confidence in the results that the cells we can identify in the blood represent hemangiosarcoma progenitors. Even if they do not, their presence seems to be infrequent in healthy dogs from a low-risk population, so we anticipate positive tests will be informative. If the cells of interest are associated with other tumors, it would mean that the test could be deployed more widely, and particularly for other tumors that we expect would be equally responsive to eBAT prevention.
3. We opened Shine On phase-3 on January 2, 2018. As of August 20, 2018, we had enrolled 78 healthy dogs (Golden Retrievers, Boxers, and Portuguese Water Dogs).
Even though we have not completed recruitment to establish sensitivity and specificity for the blood test, we have concluded from our data that the best way to determine if we can use this method to identify dogs with a high probability to eventually develop hemangiosarcoma, is to examine samples from dogs that are presumed to have “moderate risk” (based on age and breed) prospectively, and to follow these dogs through an extended period of time to determine if they eventually develop the disease. To our knowledge, this is the first time this type of bold experiment will have been done in dogs, and we believe the results will be more definitive than what we would obtain by further “tweaking” the assay in the phase-1 and phase-2 design.
By implementing secondary safeguards (additional markers to define “circulating hemangiosarcoma progenitor cells”), we believe that we will be able to protect against false positive results. As part of the modifications to the study, we have been more emphatic in our communication with potential enrollees that, like every clinical trial, Shine On phase-3 is an experiment. Our institutional and programmatic philosophy is to make sure pet owners understand that clinical trials, regardless of their nature, do not have guaranteed benefits, and so, specifically for Shine On, the study website, the enrollment form, the FAQs, and the study reports all include the following statement: “The Shine On study is not intended as a diagnostic for disease. It is an experiment to determine whether the blood test can be used as a tool for early detection of hemangiosarcoma. At this point, we do not know if a negative test result means the dog does not have, or will never get, hemangiosarcoma. We also do not know if a positive test result means that a dog will definitely get hemangiosarcoma. The study is designed to answer some of these questions.”
We have added a new parameter to the assay, using a human adenovirus that is “crippled” so it cannot replicate and cause disease, but it can still infect the putative hemangiosarcoma progenitor cells in the blood, but not normal while blood cells. We will continue developing this new parameter to further enhance the potential sensitivity and specificity of the early detection test.
Managing Shine On wholistically, and evaluating all the data in aggregate, will provide more robust data than if we were to parcel out the results by phase. This was not something we could have easily predicted in foresight, but it is clear in hindsight. In other words, since interim analyses are fraught with risk, we have decided to avoid strong conclusions from incomplete data. We will, of course, conduct a complete and thorough analysis of all the data once all the samples are collected and processed through the assays, and the results, whether positive or negative, will be reported to the AKC CHF and through them to the foundations that have supported the study. We also intend to publish the data in the peer reviewed literature. Regardless of the final result, there is significant innovation in this trial that will be of interest to the biomedical and translational communities. We are excited to document that large-scale trials for early cancer detection are feasible in companion dogs.