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Phase II open-label non-randomized multicenter clinical trial of trametinib for dogs with histiocytic sarcoma

Purpose

To determine the anti-tumor effect of trametinib, a new anti-cancer drug, in dogs diagnosed with histiocytic sarcoma

Background

Histiocytic sarcoma is an aggressive cancer in dogs. Even with treatment, most of the time the disease will spread quickly. Response rates to current treatments are usually poor.

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 collaborators at University of Florida have performed studies to identify the 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 from 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.

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 (specifically, absolute neutrophil count >2,500/μL, Hct >28%, platelets >100,000/μL, liver transaminases <3x upper limit of normal with a normal total bilirubin, serum creatinine <2x upper limit of normal, adequate clinical health (VCOG-CTCAE v2 constitutional signs of ≤1) 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

  • 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 

 

Study Design

This study takes place at the Animal Cancer Care and Research Center (ACCRC) in Roanoke, VA.

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. 

We will provide you with a calendar of study visits at the time of enrollment.

Side effects will also be evaluated at home continuously. You will be asked to fill out Quality of Life questionnaires prior to starting the study and prior to every recheck visit.

If euthanasia is elected at any point, we will ask your permission to perform a necropsy, which is the animal version of an autopsy. A necropsy will allow us to further understand the biology of this lethal disease, and may help in the development of better treatments in the future. 

Compensation

Costs associated with obtaining a diagnosis and staging the cancer are the responsibility of the owner. Trametinib will be supplied at no cost. The study will partially pay for recheck physical examination fees (up to $200), collection of blood and tumor samples for investigation, and routine laboratory tests/diagnostic imaging (chest x-rays and abdominal ultrasound) at scheduled recheck visits (up to $700/visit). Dr. Dervisis and his team will provide more details about the study financial coverage before enrollment. 

Contact

Mindy Quigley, Clinical Trials Coordinator
Office Phone: 540-231-1363 | Email: mindyq@vt.edu

Dr. Nick Dervisis, Medical Oncology
Phone: 540-526-2300 | Email: dervisis@vt.edu

If your query is urgent, please call the Animal Cancer Care and Research Center on 540-526-2300.