Arteriovenous malformation (AVM) is a tangle of abnormal vessels that can progress through life and cause significant bleeding, deformity, pain, and deficits in day-to-day activities. Surgery is a common treatment option for patients with AVMs where the goal is to safely remove the entire AVM without causing complications. While any surgery has its potential risks, most of the potential modifiable risk factors relate to the AVM's structure, such as the AVM size or presence of high risk structural features seen on scans. The purpose of this pilot study is to see whether taking an oral medication called Trametinib can improve upon the AVM structure in adult patients before their scheduled surgery.
The goal of this pilot clinical trial is to see whether an oral medication called Trametinib can be given to patients with arteriovenous malformations (AVMs) of the brain and body before surgery in order to make the AVM structure less risky for surgery. The main questions it aims to answer are: 1. does taking Trametinib make the structure of the AVM less risky for surgery? This will determined by comparing the size and structure of the AVM on repeat scans before and after taking the drug. 2. does taking Trametinib reduce the blood flow to the AVM? This will be determined by quantifying the blood flow to the AVM with quantitative magnetic resonance imaging software. 3. is the drug well tolerated in this patient population? This will be determined by following for any side effects of the medication 4. how does the drug do what it is supposed to do clinically by looking at its effect at the cell level? This will be determined by taking a piece of the AVM that is removed at the time of surgery and running experiments in the lab to compare its structure and behaviour to other AVMs that were not treated with this medication. Participants will first undergo screening tests to ensure they are candidates for the medication. They will take oral Trametinib once daily for a total of 60 days prior to their planned surgery. They will be monitored for side effects at days 15, 30 and 60. They will undergo routine scans prior to starting the drug and then again within 5 days of their last dose to see any changes made to the AVM structure after taking the drug. Lastly, at the time of surgery, a part of the AVM removed will be sent to our research lab to see what the drug is doing at the cell level to result in the changes we can see on the scans.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Drug is supplied in 2mg and 0.5 mg tablets
University Health Network
Toronto, Ontario, Canada
RECRUITINGRadiological response by independent central review at day 60 or 5 days after last dose, whichever comes first
as defined by one or more of the following: (1) at least 20% reduction in the volume of the AVM confirmed on repeat imaging, (2) resolution of angiographic weak points, or (3) resolution of AVM induced parenchymal changes by independent central review.
Time frame: screening, Day 60 or 5 days after last dose (whichever comes first)
Safety of Trametinib in surgical AVM population
Participants will be followed serially for the presence of adverse events, including their type, severity, and need for dose modifications or interruptions
Time frame: screening, Day 15, 30, 60, within 1 week of surgery and up to 30 days after final dose
Change from baseline in symptomatology and functional performance
Participants will be followed serially for any changes in self-reported clinical symptoms or signs, and for any changes in functional outcome with the modified Rankin Scale (mRS) (scale from 0 to 6, with increasing score representing worse functional status)
Time frame: screening, day 15, 30, and 60
Change from baseline in AVM blood flow
The blood flow to the AVM will be objectively compared over time after Trametinib dosing with serial quantitative magnetic resonance angiography imaging
Time frame: screening, day 60 or 5 days after final dose (whichever comes first)
Effect of Trametinib on AVM pathobiology
The documentation of signaling pathways identified in AVM tissues after Trametinib drug administration
Time frame: time of surgery
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