Pilot Study on Trametinib for Surgical Unruptured AVMs

Last updated: May 28, 2024
Sponsor: University Health Network, Toronto
Overall Status: Active - Recruiting

Phase

2

Condition

Hemangioma

Birth Defects

Holoprosencephaly

Treatment

Trametinib tablet

Clinical Study ID

NCT06098872
23-5463
OZUHN-017
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age ≥18 years.

  2. Confirmed diagnosis of an unruptured AVM Spetzler-Martin Lawton Young Grade equal toor 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 inpatient's medical history.

  3. Planned surgical resection of AVM at University Health Network within the acceptablewindow defined by the study calendar (i.e. after the indicated study drug dosingperiod and approximate week-long follow up).

  4. Patients must not have received an investigational drug within the 4 weeks prior tostudy enrolment.

  5. Patients who have previously received biologic therapy treatment must have completedtherapy at least 14 days prior to study enrolment.

  6. Patients who have previously received myelosuppressive chemotherapy must havecompleted therapy at least 28 days prior to study enrolment.

  7. Patients on anticoagulants must have stopped treatment within 7 days of startingTrametinib.

  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) andfertile men who are sexually active must agree to the use of 2 forms ofcontraception (as discussed with the overseeing physician) throughout the period ofstudy treatment and for 16 weeks after last dose of study drug. They are not allowedto donate ova or sperm for up to 16 weeks after the last dose of study drug.

Exclusion

Exclusion Criteria:

  1. AVM due to known germline mutation such as phosphatase and tensin homolog (PTEN) orknown 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 overseeingInvestigator, within 28 days prior to study enrolment or who have not recovered fromside 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 7days of enrolment.

  9. Retinal vein occlusion, serous retinopathy or glaucoma diagnosed within 1 month ofenrolment.

  10. Diagnosis of significant liver failure (Child-Pugh score 2+) within 7 days ofenrolment.

  11. Rhabdomyolysis (creatinine kinase (CK) >5x ULN) within 7 days of enrolment.

  12. Patients with known risk factors for gastrointestinal perforation (priorperforation, diverticulitis, metastases to the gastrointestinal tract andconcomitant use of medications with a recognized risk of gastrointestinalperforation

  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 bythe overseeing Investigator.

Study Design

Total Participants: 10
Treatment Group(s): 1
Primary Treatment: Trametinib tablet
Phase: 2
Study Start date:
January 30, 2024
Estimated Completion Date:
November 30, 2025

Study 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.

Connect with a study center

  • University Health Network

    Toronto, Ontario
    Canada

    Active - Recruiting

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