Pilot Study on the Efficacy of MEK1/MEK2 Inhibitor Trametinib in Patients With Surgical Unruptured Arteriovenous Malformations

23-5463

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.

2024-01-30

2025-11-01

2025-11-01

Recruiting

Early phase I

10

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': '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.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ESTIMATED'}}

2024-05-30