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Modulating the Immune Microenvironment in Canine Osteosarcoma

Status: Recruiting

Species: Dog

Veterinary Speciality: Oncology

Description

The purpose of this study is to evaluate the use of a new immune therapy in dogs with osteosarcoma, a malignant tumor that affects the long bones in dogs. The standard treatment for dogs with osteosarcoma is amputation of the affected limb followed by generally 4 treatments with a chemotherapy drug called carboplatin. Unfortunately, 25-30% of affected dogs will develop spread of the osteosarcoma to the lungs before chemotherapy treatment is completed, and 50% of all dogs will have spread within 6-8 months following amputation.  Only 15% of dogs will live for two years after amputation. Therefore, new therapies for this cancer are desperately needed. There is increasing evidence that the immune system can recognize and kill osteosarcoma cells. A few recent studies in dogs with osteosarcoma using different ways to stimulate the immune system have been promising. However, most of them are not used until after the amputation/surgical site has healed or until after the chemotherapy treatments have been finished. This gives the remaining tumor cells a chance to continue growing and find ways to evade the immune system. The purpose of this study is to use a new method to stimulate the immune system during the immediate time period after amputation. This is the time when remaining tumor cells are most vulnerable to attack. To do this, an immune stimulant is placed in the surgical site where it works to stimulates immune cells during healing with the goal of killing any remaining tumor cells before they can start growing again. In this study, we will use a drug called resiquimod (also known as R848). This drug has been studied in dogs and people to treat cancer and help the immune system clear viral infections. In the previous dog study, direct injection of the drug into the tumor caused some of them to shrink for a long period of time. Importantly, the treatment was very well tolerated by dogs with no side effects related to the resiquimod.  In the current study, the goal will be to kill any residual tumor cells in the body following surgery, rather than trying to make a large tumor shrink. Briefly, the resiquimod is embedded in a hydrogel that is placed at the amputation surgery site before it is closed. This allows the resiquimod to be slowly released over 7-14 days while the surgery site is healing. The resiquimod is a very strong stimulant that activates immune cells both at the surgery site as well as in lymph glands draining the area where tumor cells may have escaped. Studies using this method in mouse models of cancer have been very promising, with the resiquimod able to prevent local regrowth and spread of tumor cells. We are therefore hopeful that this approach will have similar results in dogs.

Inclusion Criteria

Eligible patients (any breed of dog) must meet all of the following criteria:

  • Dogs diagnosed with cytologically confirmed appendicular osteosarcoma
  • Dogs must be at least 1 year of age and body weight of 10 kg or higher
  • Adequate organ function as indicated by standard laboratory tests (complete blood count, serum biochemistry profile, urinalysis)
    • ANC ≥ 2000/μL and platelet count ≥ 100,000/μL
    • Liver: Total bilirubin ≤ 1.5X the institutional upper limit of normal (ULN), ALT ≤ 3X ULN
    • Renal: Serum creatinine ≤ 1.5X ULN
    • ECOG performance score of 0-1
  • Otherwise medically healthy with no underlying clinically significant cardiac, renal, or hepatic disease
  • Dogs must have an estimated life expectancy of at least 28 days
  • Informed written consent must be obtained

Exclusion Criteria

Patients (dogs) meeting any of the following criteria will not be eligible for the study:

  • Pregnant or lactating dogs
  • Evidence of metastatic disease
  • Dogs must not have received a prior immunotherapy regimen
  • Concurrent use of complementary/alternative medicines that in the opinion of the principal investigator would confound the interpretation of activity of the study drug
  • Dogs with significant cardiovascular disease
  • Less than 2 weeks from a major surgical procedure
  • Any serious systemic disorder incompatible with the study (at the discretion of the principal investigators)

Client Benefits

The potential benefit to your dog is that the resiquimod will activate your dog’s immune system to kill remaining cancer cells and prevent tumor spread to the lungs or other parts of the body. This would then help your dog to live longer after amputation.

The study will cover the office visit, x-rays, needle aspiration of the tumor for diagnosis, and bloodwork prior to amputation to determine eligibility. The study will cover $1500 of the approximate $3000-3500 total cost for amputation of the affected leg. The study will also cover all of the costs associated with chemotherapy, bloodwork, and x-rays following amputation for up to one year (12 months) after amputation such as delayed healing of the surgery site. The study will cover costs related to complications associated with the resiquimod hydrogel. The study will not cover costs associated with complications secondary to the carboplatin chemotherapy (i.e., antibiotics for low white blood cell count, hospitalization from side effects from the carboplatin chemotherapy). The study will not cover costs associated with conditions unrelated to the osteosarcoma treatment (skin infection, ear infection, etc.).

Sample or Data Requirements

At the time of amputation a hydrogel containing resiquimod will be placed into the surgical site between the muscle layers.  As the hydrogel dissolves, it releases the resiquimod slowly, activating immune cells in the lymph glands draining the surgery site to hopefully help kill any remaining osteosarcoma cells that may have escaped from the tumor.  You dog will then go on to receive standard treatment for osteosarcoma consisting of 4 doses of carboplatin chemotherapy (one treatment every 3 weeks).  Your dog will be followed for evidence of tumor spread by taking chest x-rays every 2 months.  We will follow your dog’s bloodwork to check cell counts and make sure that the liver and kidneys are functioning normally.  At each treatment, we will also collect a blood sample (approximately 1-2 tablespoons) that will allow us to look for markers that indicate response to treatment.  The specific details of the procedures and office visits associated wtih the study are found in the “Study Calendar” on the last page of the consent form.

Contact Info

For questions regarding the clinical trial please email the clinical trials technician, Diane Welsh at: clinicaltrials@tufts.edu

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