Our overall objective is to determine a clinically optimal dose and estimate the efficacy of propranolol in dogs with hemangiosarcoma when given as an adjunct to chemotherapy. Specifically:
Objective 1: We will confirm the tolerability and estimate the clinical benefit of propranolol in combination with doxorubicin.
Objective 2: We will assess levels of propranolol in the bloodstream after long-term administration to dogs with hemangiosarcoma to determine if there is a correlation between drug levels in blood and overall survival. We will also determine if propranolol alters the blood levels (exposure) of doxorubicin in dogs receiving propranolol and compare these levels to those found in the published literature for dogs receiving doxorubicin. Collection of these data will allow us to better understand how these drugs may be working together.
We opened the trial on July 1, 2019. As of December 31, 2022, we have screened 51 dogs and enrolled 19 dogs in the study and no dose limiting toxicities within the initial 21-day assessment period have been observed. Based on these results, we are continuing to enroll dogs at the highest dose of propranolol (1.3 mg/kg) being tested. We did observe an adverse event in one dog at approximately month 6 of the protocol that could be attributed to propranolol (2-3 episodes of fainting/collapse), which was resolved by reducing the dose of propranolol to 1.0 mg/kg.
Propranolol and doxorubicin levels in the blood from 18 of the dogs enrolled to date have been analyzed. Analysis of samples from dog 19 is pending.
Currently three dogs enrolled in the study are alive while sixteen dogs have died. Of the dogs that died, two dogs were euthanized due to health issues unrelated to recurrence of hemangiosarcoma. So far, five of the nineteen dogs have survived for more than nine months (26.3%). Of these five dogs, four have survived for more than one year (21.1%), and two of these dogs have survived for more than three years (10.5%).
We plan to enroll the final dog in the study within the next six months at either the University of Pennsylvania or Purdue University.
We also plan to complete the analysis of drug levels (propranolol and doxorubicin) in the blood samples. Analysis of the samples from eighteen dogs has been completed, and the analysis from dog nineteen is pending. We may need to request an additional no cost extension for the study depending on when the final dog is enrolled.
