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Evaluation of a recombinant, attenuated Listeria vaccine following standard of care therapy in newly diagnosed dogs with appendicular osteosarcoma

Objective:

To investigate whether the listeria vaccine administered (3x) following Standard of Care therapy improves long-term disease control in canine appendicular osteosarcoma patients at OVC HSC.

Study Summary:

This study is investigating the addition of the listeria vaccine to standard of care (amputation followed by adjuvant carboplatinum chemotherapy) for canine appendicular osteosarcoma. This study will discover if pulmonary metastases can be inhibited or delayed (with improved survival time) by monitoring patients with physical exams and imaging (chest radiographs).

Multiple studies of human OSA samples have revealed that the epidermal growth factor receptor HER2/neu is expressed in both primary and metastatic lesions and that HER2/neu serves as a relevant target for T cell mediated therapies. An attenuated, recombinant Listeria vaccine containing HER2/neu was created to be able to induce HER2 specific immunity, prevent metastatic disease and prolong overall survival in dogs with OSA following amputation and carboplatin. A phase I safety study was performed and overall survival rates at 1, 2 and 3 years for dogs treated with this vaccine were 78%, 61% and 50% respectively (Mason et al., 2016). In comparison, 1-2yr survival rate is only 15% following current standard of care (amputation and chemotherapy).

This promising result suggests that the listeria vaccine safely induces potent immunity that contributes to the delay or prevention of metastatic disease and possible delay of primary disease progression. Based on the results generated from this work, this listeria vaccine was granted orphan drug designation for OSA by the FDA in May 2014 and fast track designation from the FDA for pediatric OSA in April 2016. Furthermore, a phase I clinical study for the treatment of human adult patients with HER2/neu+ metastatic solid tumors was approved in Jan 2015 and this trial is currently accruing patients (ClinicalTrials.gov Identifier: NCT02386501).

Inclusion Criteria:

  • Diagnosis of appendicular osteosarcoma (histological/cytological)
  • Dogs > 25kg
  • Disease that is amenable to surgical removal via amputation
  • No evidence of metastasis – physical exam, chest radiographs & abdominal ultrasound
  • No previous therapy for osteosarcoma
  • No significant co-morbid illness (including renal/hepatic failure, heart failure/clinical coagulopathy)
  • Commitment to attend  all OVC HSC required appointments & planned treatments
  • Dogs must undergo post-mortem examination if they die during study period

Incentives:

  • Once enrolled at OVC HSC, chest radiographs & physical examinations at no cost to owner (paid by study) and access to the listeria vaccine which is not otherwise available in Canada

Samples required:

  • Blood & Urine (at time of enrollment & then at various time points throughout the study period)
  • Chest radiographs (at time of enrollment & then every 8 weeks (for 7 months)

For further information please contact:

Dr. Vicky Sabine (PhD), Clinical Research Coordinator

Email address: clinical.research@uoguelph.ca

Work cell #: 226-218-0338

Websites: http://ovc.uoguelph.ca/icci/

http://www.ovc.uoguelph.ca/hsc/en/aboutovchealthsciences/ClinicalTrials.asp

 

Funded by: NIH COTC (https://ccrod.cancer.gov/confluence/display/CCRCOPWeb/Home) and Sponsored by: Morris Animal Foundation.