Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

Sponsor

Stanford University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04258046

Collaborator

Boston Children's Hospital (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Arteriovenous malformation (AVM) is a congenital vascular anomaly that progresses throughout life and causes complications including tissue destruction due to rapid overgrowth, bleeding, functional deficits, severe deformity and cardiac failure. Unfortunately, traditional managements have transient benefits with more than 90 recurrence rate within a year. Therefore, there is a significant unmet medical need. The purpose of this study is to assess the safety and efficacy of Trametinib in children and adults with Extracranial Arteriovenous Malformation (AVM).

Condition or Disease	Intervention/Treatment	Phase
Venous Malformation Arterial Disease	Drug: Trametinib tablet	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Clinical Trial of MEK Inhibitor Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation (VM)

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Trametinib Patients will receive oral trametinib once daily	Drug: Trametinib tablet Drug is supplied in 0.5 mg and 2 mg tablets

Arm

Intervention/Treatment

Experimental: Oral Trametinib

Patients will receive oral trametinib once daily

Drug: Trametinib tablet

Drug is supplied in 0.5 mg and 2 mg tablets

Outcome Measures

Primary Outcome Measures

Disease response rate by investigator assessment at Month 6 [Month 6]
Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.

Secondary Outcome Measures

Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area [Month 6]
Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area [Month 12]
Disease response rate by investigator assessment at Month 12 [Month 12]
Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must be ≥ 12 years and ≤ 60 years
Confirmed diagnosis of complicated extracranial AVMs made by a physician who is familiar with this condition.
Genetic testing for mutations within MAP2K1 or remaining RAS/MAPK pathway is preferred but not mandatory
Patient is able to swallow and/or retain oral medication via G tube
All clinical and laboratory studies to determine eligibility will be performed within six weeks prior to enrollment unless otherwise indicated.
Patients who have undergone surgical resection or interventional radiology procedures (sclerotherapy) of their AVM are eligible if they meet all inclusion criteria after these procedures
At least 4 weeks from undergoing any major surgery
Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.
Myelosuppressive chemotherapy: None within 4 weeks of entry into this study.
At least 14 days since the completion of therapy with a biologic. For agents that have known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur. These patients must be discussed among PI and other investigators on a case-by-case basis.
Patients must not have received an investigational drug within the prior 4 weeks.
Not within 6 months prior to entering study if AVM is within field of radiation

Exclusion Criteria:

AVM due to germline mutation such as PTEN
Prior MEK inhibitor therapy or have allergy or contraindication to MEK inhibitor
Unable to swallow PO drugs or administer the drug via G tube
Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such procedure
Patients with evidence of or history of cardiovascular risk
Patients with retinal vein occlusion, hemorrhage or have a history of such conditions.
Patients who are currently on other immunosuppressive medication(s)
Patients who have an uncontrolled infection
Unstable health status that may interfere with completing study
Unable to travel to clinic as requested
Patients unwilling or unable to comply with the protocol, or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
Females of child-bearing potential must be willing to practice acceptable methods of birth control.
Additionally, females of childbearing potential must have a negative serum pregnancy test result from 7 days prior to the initiation of the medication to 3 months after the final administration of the medication. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the period when they are receiving the study drug and for 3 months thereafter.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pediatric Dermatology Clinic at Stanford Children's Hospital	Palo Alto	California	United States	94304

Sponsors and Collaborators

Stanford University
Boston Children's Hospital

Investigators

Principal Investigator: Joyce Teng, MD, PhD, FAAD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Joyce Teng, Director of Pediatric Dermatology, Stanford University

ClinicalTrials.gov Identifier:

NCT04258046

Other Study ID Numbers:

53105

First Posted:

Feb 6, 2020

Last Update Posted:

Mar 14, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Congenital Abnormalities

Trametinib

Study Results

No Results Posted as of Mar 14, 2022