Clinical trial using immunotherapy with surgery for dogs with osteosarcoma
Clinical trial to evaluate the safety and effectiveness of ELIAS Cancer Immunotherapy combined with surgery as treatment for appendicular osteosarcoma in dogs
Purpose and Brief Study Description:
Osteosarcoma comprises 5-10% of canine cancers. At least 75% of canine bone cancers are osteosarcomas. It is estimated that there are 8,000-10,000 new cases of canine osteosarcoma diagnosed in the U.S. annually. Currently, amputation followed by carboplatin chemotherapy is the “standard of care” for treating canine patients with osteosarcoma. Carboplatin is a chemotherapy agent approved for use in people. Reported median survival times for dogs treated with amputation surgery followed by 4 doses of carboplatin chemotherapy is 10-12 months. Although this is longer than what is reported with tumor removal (amputation) alone, additional therapies are warranted for this aggressive tumor in dogs.
The primary purpose of this study is to demonstrate the safety and efficacy of a new combination therapeutic protocol, ELIAS Cancer Immunotherapy (ECI-OSA-04) combined with surgery as treatment for appendicular osteosarcoma in dogs. The ECI-OSA-04 protocol includes a type of immunotherapy which utilizes an autologous tumor vaccine (vaccine made from the patient’s own tumor cells), collection of the patient’s tumor specific T cells, expansion of those T-cells outside the body, and then infusion of the tumor specific T-cells back to the patient with the intent for the patient to develop a long-term tumor-specific immune response.
What does enrollment into this trial involve?
Dogs that have been diagnosed with appendicular osteosarcoma, weigh >15kg (~33 pounds) and have not had surgery or received any chemotherapy are potentially eligible for this study. If your dog is eligible to participate in this clinical trial, he/she will be randomized to one of two treatment groups. Both groups will receive amputation of the limb and then one treatment group will be treated with standard-of-care carboplatin chemotherapy and the other group will be treated with the investigational ELIAS Cancer Immunotherapy combination treatment protocol (ECI-OSA-04).
During the Screening Phase, all dogs will first undergo staging of their osteosarcoma (to include blood work, urinalysis and chest x-rays) to ensure they don’t have metastatic disease and to further confirm study eligibility. Following staging, dogs will be scheduled to undergo amputation of the affected limb. After amputation, part of the cancer tissue will be submitted for histopathology to confirm diagnosis and the remaining cancer tissue will be used to make the autologous tumor vaccine. To be eligible to advance to the treatment protocol, enough cells to generate sufficient tumor vaccine for the planned vaccination series must be present. If enough cells are not generated within an allowable 3 week time period, your dog cannot advance and will be removed from the study. Eligible dogs will be randomized to treatment group following surgery and histologic tumor confirmation and also after the cancer tissue harvested has been determined to meet the tissue acceptance criteria. Dogs will be randomized at a 1:1 ratio where half of the dogs will be randomized to the carboplatin chemotherapy treatment arm and half to the Elias Cancer Immunotherapy treatment arm.
Carboplatin treatment :
During the Treatment Phase, if your dog is randomized to receive carboplatin treatment, he/she will receive four doses of chemotherapy once every three weeks. Treatment will start approximately 2 weeks after surgery on Days 14, 35, 56 and 77 of the study. Additionally, on Days 21 and 28 we will perform blood work to monitor for chemotherapy side effects. We will also repeat blood work prior to each chemotherapy to ensure your dog has adequate blood counts to receive treatment. We may need to delay chemotherapy by 3-7 days depending on the results of the blood work. During the Treatment Phase, we will ask you about any adverse events your dog experienced since the previous visit, if he/she has started any new medications, and have you complete a Quality of Life (QOL) survey at each treatment visit.
During the Follow-up Phase, we will continue to monitor your dog’s progression on study at 5 months, 8 months, 11 months, 13 months, 15 months and 18 months after surgery. During these visits, we will perform a physical examination and repeat chest x-rays to ensure he/she is still in remission. We will ask you about any adverse events your dog experienced since the previous visit, if he/she has started any new medications, and have you complete a QOL survey at each follow-up visit. If your dog completes the study, his/her study participation will end at the 18 month follow-up visit.
ELIAS Cancer Immunotherapy ( ECI-OSA-04) treatment :
During the Treatment Phase, approximately 1 week following surgery, the ECI-OSA-04 therapy will begin. Briefly, the ECI-OSA-04 protocol includes vaccination of your dog with an autologous tumor vaccine, collection of tumor specific T-cells from your dog by a procedure called apheresis, expansion of those T-cells by a process done in a laboratory, re-infusion of the expanded tumor specific T-cells back into your dog and then treatment with IL-2 to help continued expansion of the tumor-specific T-cells within your dog.
More specifically:
Vaccinations: a course of three vaccinations will be administered at weekly intervals starting approximately 1 week after surgery (on Days 7, 14 and 21 of the study). Initiation of the treatment protocol (first vaccination) may be delayed up to an additional 2 weeks (Days 21, 28 and 35) if there is a need for additional time to culture the harvested cancer cells to generate sufficient cells for vaccine. The subsequent treatment protocol (i.e., Apheresis, T cell infusate, etc.) will also be delayed up to 2 weeks. During this period we will perform a physical examination, blood work, ask you about any adverse events your dog experienced since the previous visit, if he/she has started any new medications, and have you complete a Quality of Life (QOL) survey at each treatment visit.
Apheresis will be performed to collect tumor-specific T lymphocytes from your dog’s blood one week after the final vaccination (on Day 35). Apheresis is a procedure that is used in the treatment of various conditions in people and it is similar to dialysis. A specific machine designed for this use is utilized to circulate the patient’s blood to remove the T-cells from the blood stream
The T cell infusate, the end product generated from the cells collected by the apheresis procedure, will be re-infused into your dog one week later, on Day 42. Prior to the T cell infusion, we will also do a physical examination, blood work, ask you about any adverse events your dog experienced since the previous visit, if he/she has started any new medications, and have you complete a QOL survey.
IL-2 administrations will be given to increase the immune response. IL-2 will be injected subcutaneously (under the skin) beginning 24 – 48 hours following the T cell infusion of activated T cells in order to continue to stimulate T cell multiplication in your dog for a prolonged period of time. Subsequent doses of IL-2 will be given at ~48-hour intervals for a total of 5 injections.
During the Follow-up Phase, we will continue to monitor your dog’s progression on study starting 1 week after the last IL-2 injection (Day 56) and 5 months, 8 months, 11 months, 13 months, 15 months and 18 months after surgery. During these visits, we will perform a physical examination and repeat chest x-rays to ensure he/she is still in remission. We will ask you about any adverse events your dog experienced since the previous visit, if he/she has started any new medications, and have you complete a QOL survey at each follow-up visit. If your dog completes the study, his/her study participation will end at the 18 month follow-up visit.
Client Compensation:
Once informed consent is obtained and a preliminary diagnosis of appendicular osteosarcoma is confirmed, this trial provides funding for all treatment-related costs. These costs include imaging, bloodwork, surgery, chemotherapy and all costs associated with the ECI-OSA-04 therapy, including, vaccine development and administration, apheresis for T cell collection, T cell infusion and IL2 administration as well as management of adverse events that are possibly attributed to therapy.
Contact Information:
Please contact Kris Richardson, Clinical Trials Coordinator at the Veterinary Health Center, for more information about this study. Phone: (785)-532-3046; email: ClinicalTrials@vet.k-state.edu