Exploratory study of an oral blood-brain barrier penetrant, procaspase-3 activator (PAC-1) in combination with hydroxyurea for treatment of canine meningioma

Purpose

To determine whether treatment with the oral chemotherapy drug procaspase-3 activator (PAC-1), in combination with the oral drug hydroxyurea, can provide safe and effective treatment of canine meningiomas.

Background

Brain tumors are a significant cause of illness and death in dogs, with meningioma accounting for approximately half of the cases diagnosed in pet dogs. Although surgery remains the best treatment dogs with meningioma, some dogs are not good candidates for this. In these situations, effective treatment options are limited. To address this gap, we are running a pilot clinical study to determine the safety and effectiveness of a new chemotherapy approach. Dogs in this study will receive an experimental combination of PAC-1 and hydroxyurea, followed by surgery to remove their tumor. Tumors will be analyzed to see if the drug combination was effective in reaching and targeting their tumors. We hope to determine if the experimental drug combination can provide an alternative treatment for dogs whose tumors cannot be surgically removed.

Eligibility

  • Dogs of any breed, age, or sex
  • MRI-confirmed diagnosis of a solitary, extra-axial forebrain mass lesion with imaging characteristics consistent with a meningioma (cerebral convexity, falcine, parasagittal) that is amenable to surgical resection
  • Measurable tumor (>10 mm diameter)
  • Stable or decreasing dose of corticosteroids, and if applicable, seizures controlled with antiepileptic medication

Exclusion

  • Dogs with significant preexisting renal, hepatic or cardiac disease, a history of poor performance under general anesthesia, or a history of prior radiotherapy or use of cytotoxic chemotherapy
  • Dogs with cystic olfactory lobe lesions
  • Dogs with uncontrolled seizures

Study Design

Enrolled dogs will have an initial visit including physical exam, bloodwork, and an MRI at the Veterinary Teaching Hospital in Blacksburg, VA. Dogs will begin taking oral prednisone, if they are not already receiving it. The investigational treatment in this study is a combination of oral chemotherapy agents (PAC-1 + hydroxyurea). At Day 14, Day 21, and Day 42, dogs will travel to the NIH National Cancer Institute to have the chemotherapy treatment monitored with non-invasive molecular brain imaging techniques. Interim rechecks will be performed in Blacksburg on Days 11, 18, 28, and 42. At the conclusion of the study period (Day 43), dogs will undergo surgical tumor removal. Dogs will be hospitalized for 2-3 days following tumor removal.

Please note: PET scans and chemotherapy treatment at 14, 21, and 42 days post-treatment will take place at the NIH National Cancer Institute facility in Bethesda, MD.

    The following visit schedule is required for all enrolled dogs:

  • Day 1 | Enrollment visit & MRI | Veterinary Teaching Hospital, Blacksburg, VA
  • Day 11 | Recheck visit | Veterinary Teaching Hospital, Blacksburg, VA
  • Day 14 | MRI/PET/CT scan | NIH, NCI, Bethesda, MD
  • Day 18 | Recheck visit | Veterinary Teaching Hospital, Blacksburg, VA
  • Day 21 | MRI/PET/CT scan | NIH, NCI, Bethesda, MD
  • Day 28 | Recheck visit | Veterinary Teaching Hospital, Blacksburg, VA
  • Day 40 | Recheck visit | Veterinary Teaching Hospital, Blacksburg, VA
  • Day 42 | MRI/PET/CT scan | NIH, NCI, Bethesda, MD
  • Day 43-45 | Tumor removal surgery | Veterinary Teaching Hospital, Blacksburg, VA

Compensation

Owner is responsible for the cost of obtaining an MRI to confirm diagnosis. Once the diagnosis is confirmed and the dog is enrolled, all treatment and follow-up examinations related to this study will be provided at no cost during the study period. Owners are responsible for travel-related expenses and medication costs associated with ongoing seizure control, if required.

Contact

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

Dr. John Rossmeisl, Principal Investigator, Professor, Neurology/Neurosurgery
Phone: 540-231-3239

If your query is urgent, please call the Small Animal Hospital on 540-231-4621 and ask for the neurologist on duty.