This study investigates a new anti-cancer drug, trametinib, that specifically targets growth signals found in cancer cells of dogs. Trametinib is FDA-approved for use in people, and our previous studies have identified a safe dose for dogs.

This study will determine the anti-tumor effect of trametinib in dogs diagnosed with histiocytic sarcoma. We hope that this new treatment, which is still experimental in dogs, will decrease the size of the cancer, improve the patients' outcomes, and increase their life expectancy. Additionally, the study will test whether markers in the cancer cells’ genes can predict the response to treatment. This information could be used in the future to help select those dogs that are more likely to respond positively to treatment.

This study is funded by the Morris Animal Foundation and supported by The Bernese Mountain Dog Club of America.

Eligibility:

• Dogs of any age, weight, sex, or breed with a cytological or histological diagnosis of histiocytic sarcoma
• Dogs with measurable tumors (primary or metastatic)
• Dogs with an estimated life expectancy of >4 weeks
• Participation in the study will be offered when conventional therapy is no longer effective or is declined by the dog’s client-caregiver.
• Signed informed consent and consent to necropsy will be obtained at time of enrollment.
• No prior chemotherapy within a minimum 2-week period
• No prior radiation therapy within a minimum 1-month period
• Dogs with adequate organ and marrow function and without serious systemic disorders that could compromise the patient’s health
• Dogs with a prior or concurrent cancer whose prognosis or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen

Exclusion Criteria:

• Dogs receiving any concurrent antineoplastic therapy will be excluded
• Prior chemotherapy within the past 2 weeks
• Prior radiation therapy within the past 1 month
• Patients who are clinically ill from their metastatic tumors and have a life expectancy of under 4 weeks

Treatment:

Dogs diagnosed with histiocytic sarcoma that fulfill the inclusion/exclusion criteria will be invited to enroll in this clinical trial. Prior to treatment, a tumor biopsy, and a blood sample (less than 1 ounce) will be collected. Upon enrollment, every patient will undergo a complete history, physical examination, laboratory analysis, blood pressure measurement, and diagnostic imaging (radiographs, and abdominal ultrasound). Trametinib will be administered orally at home, once daily, for as long as the drug is well tolerated and the tumor does not progress.

Your dog will need to return for evaluation of tumor response and/or monitoring of side effects at week 2, then every 4 weeks until week 14. After that, your dog will return every 8 weeks, until there is evidence of disease progression. On week 2, your dog will be evaluated via physical examination, bloodwork, and tumor size measurements. Starting on week 4, and every other 4 weeks until week 14, blood and urine samples will be taken, and x-rays and abdominal ultrasound will be repeated to monitor your dog’s response to treatment. Starting on week 14, these rechecks will be spaced out to every 8 weeks.

Cost:

Trametinib will be supplied at no cost. The study will pay for recheck physical examination fees, collection of blood and tumor samples for investigation, and routine laboratory tests/diagnostic imaging (chest x-rays and abdominal ultrasound) at scheduled recheck visits.

Contact:

For additional information or to inquire about participation, contact the Oncology service at cvm.oncoinfo@msu.edu. All patients must first be evaluated by our Oncology service via referral. See the MSU Veterinary Medical Center referral form here.