Pilot Study on Trametinib for Surgical Unruptured AVMs

Trial Title: Pilot Study on Trametinib for Surgical Unruptured AVMs

NCT ID: NCT06098872

Condition: Arteriovenous Malformations

Conditions: Official terms:
Hemangioma
Arteriovenous Malformations
Congenital Abnormalities
Trametinib

Conditions: Keywords:
Trametinib
Mitogen-activated-protein-kinase (MEK) inhibitor

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: This is an open-label pilot study assessing the potential efficacy of Trametinib in improving AVM angioarchitecture for patients who are already planned to undergo surgical resection as part of their standard of care.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Trametinib tablet
Description: Drug is supplied in 2mg and 0.5 mg tablets
Arm group label: Experimental: Oral Trametinib

Summary: 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.

Detailed description: 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Age ≥18 years. 2. Confirmed diagnosis of an unruptured AVM Spetzler-Martin Lawton Young Grade equal to or less than 6 on magnetic resonance imaging (MRI), CT-angiogram (CTA) or angiogram, and clinical exam by a physician who is familiar with this condition at any time in patient's medical history. 3. Planned surgical resection of AVM at University Health Network within the acceptable window defined by the study calendar (i.e. after the indicated study drug dosing period and approximate week-long follow up). 4. Patients must not have received an investigational drug within the 4 weeks prior to study enrolment. 5. Patients who have previously received biologic therapy treatment must have completed therapy at least 14 days prior to study enrolment. 6. Patients who have previously received myelosuppressive chemotherapy must have completed therapy at least 28 days prior to study enrolment. 7. Patients on anticoagulants must have stopped treatment within 7 days of starting Trametinib. 8. Patient is able to swallow oral medication and/or retain oral medication via G tube. 9. Patients of childbearing potential (as assessed by their local Investigator) and fertile men who are sexually active must agree to the use of 2 forms of contraception (as discussed with the overseeing physician) throughout the period of study treatment and for 16 weeks after last dose of study drug. They are not allowed to donate ova or sperm for up to 16 weeks after the last dose of study drug. Exclusion Criteria: 1. AVM due to known germline mutation such as phosphatase and tensin homolog (PTEN) or known history of familial AVM syndromes. 2. Received prior map kinase (MEK) inhibitor therapy. 3. Known allergy or contraindication to MEK inhibitor treatment. 4. Patients who have undergone major surgery, as defined by the overseeing Investigator, within 28 days prior to study enrolment or who have not recovered from side effects of such a procedure. 5. Patients that are currently pregnant or breastfeeding. 6. A known history of coagulopathy and/or current use of anticoagulant therapy. 7. International normalized ratio (INR) > 1.5 within 7 days of enrolment. 8. Left ventricular ejection fraction (LVEF) <50%, or any ECG abnormalities within 7 days of enrolment. 9. Retinal vein occlusion, serous retinopathy or glaucoma diagnosed within 1 month of enrolment. 10. Diagnosis of significant liver failure (Child-Pugh score 2+) within 7 days of enrolment. 11. Rhabdomyolysis (creatinine kinase (CK) >5x ULN) within 7 days of enrolment. 12. Patients with known risk factors for gastrointestinal perforation (prior perforation, diverticulitis, metastases to the gastrointestinal tract and concomitant use of medications with a recognized risk of gastrointestinal perforation 13. Positive covid-19 polymerase chain reaction (PCR) test within 7 days of enrolment. 14. Patient is unwilling or unable to comply with study requirements. 15. Unstable health status that may interfere with completing the study, as assessed by the overseeing Investigator.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University Health Network

Address:
City: Toronto
Country: Canada

Status: Recruiting

Contact:
Last name: Ivan Radovanovic, MD PhD
Email: ivan.radovanovic@uhn.ca

Contact backup:
Last name: Ann Mansur, MD
Email: ann.mansur@uhn.ca

Start date: January 30, 2024

Completion date: November 2025

Lead sponsor:
Agency: University Health Network, Toronto
Agency class: Other

Source: University Health Network, Toronto

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06098872