24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs

NCT07549646 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB 24-022959GRT-00005473
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway driven vascular anomalies (VA). Trametinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. Its use in this study is considered experimental because the FDA has not approved the study drug for treating people with VAs. The study will enroll participants 2 months of age up to 30 years of age that have been diagnosed with Ras/MAPK pathway driven vascular anomalies. Study participation will last up to 3 years and will involve regular study visits to Children's Hospital of Philadelphia (CHOP) Philadelphia Campus. Participants will need to take the study drug Trametinib for at least 2 years, or up to 3 years in total, if there is a positive response. Participating in this research means you will attend up to 16 clinic visits. Most visits will take approximately 30 minutes, but some visits will take approximately 2 hours, because you will be asked to complete questionnaires about your experience. Participating in this research also means taking the study drug, having pictures taken, and completing study drug diaries. There is also an optional portion to this study that involves collecting blood for biomarker testing.

Conditions

Ras/MAPK Pathway Vascular Anomalies; Vascular Anomalies; Vascular Anomaly

Keywords

trametinib; vascular anomalies; complex vascular anomalies; Ras/MAPK pathway; CaNVAS; MEK inhibitor

Outcome Measures

Primary Outcomes (3)

• Percentage of subjects with a Substantial Response or Intermediate Response to Trametinib using an Individualized Response Criteria

  Individualized Response is a composite outcome determined by the combined results of the following 3 distinct study assessments after cycle 6: Radiologic evaluation, PROMIS Patient reported outcome (PRO) measurements, and Clinical Benefit Assessments (CBA). The results of these 3 distinct assessments will be evaluated using a set of specific criteria to determine the Individualized Response to treatment (i.e. "Substantial Response" = Improvement in Radiologic assessment by 20%, AND improvement in Global Health PROs by 3T-score points, AND improvement in at least 1 CBA, AND no clinically meaningful worsening of disease). Each subject will be determined to have: 1) Substantial Response, or 2) Intermediate Response, or 3) Stable disease, or 4) Worsening disease. A subject that is found to have a Substantial Response or Intermediate Response is considered to have a "beneficial response." Statistical analyses will be run to determine the percentage of subjects with a beneficial response.

  Individualized Response Criteria will be evaluated after 6 cycles (each cycle is 28 days) and then every 6 months until the end of the study (approximately 1.5 years)

• Relative size of target lesion(s) as determined by radiologic assessment

  \*\*For subjects with radiologically evaluable disease only\*\* The target lesion(s) will be measured at screening using imaging modality of choice based on underlying vascular anomaly (e.g. Magnetic Resonance Imaging (MRI), Magnetic Resonance Lymphangiography (MRL), US, X-rays, CT scan). MRI or MRL imaging will be recommended as primary imaging modality. For subjects with disease manifestation better characterized by alternative quantitative imaging modality (e.g. X-ray or ultrasound) this may be substituted and used as alternative imaging. Up to 3 lesions will be identified as target lesions and recorded and measured at screening. The same method of assessment and the same technique will be used to characterize each target lesion at the specified follow-up timepoints. CBA can be substituted for radiologic evaluation in subjects without radiologically evaluable disease.

  Measured at screening and after cycles 6, 12, and 24. Each cycle is 28 days.

• Quality of life as evaluated by PROMIS Patient Reported Outcome (PRO) questionnaire T-scores

  Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires will be distributed to subjects and caregivers (if applicable.) A raw score will be calculated for each PROMIS subscale. Raw scores will then be translated into a T-score metric with mean of 50 (standard deviation of 10). A higher T-score means more of the outcome being measured. Global health measures will be used as the primary outcome. Change in quality of life will be evaluated \& applied to the Individualized Response Criteria using the PROMIS global health T-scores.

  Begin at screening and after cycles 6, 12, and 24. If subject enters extension phase, will continue to measure every 6 cycles until end of therapy (approximately 1 year). Each cycle is 28 days.

Study Arms (1)

Main Study

EXPERIMENTAL

This arm will determine the proportion of subjects with an objective beneficial response to trametinib at the end of cycle 6 using an individualized response criterion based on radiologic assessment, Patient Reported Outcomes (PROs) and Clinical Benefit Assessment (CBA). It will also determine the safety of oral trametinib in children and young adults with Ras/MAPK pathway driven vascular anomalies through various laboratory testing and clinical observations.

Drug: Trametinib

Interventions

Trametinib DRUG

Subjects will receive oral trametinib daily in continuous 28-day cycles at 0.025 mg/kg/day with a maximum dose of 2 mg. A single dose reduction will be permitted in individual subjects who experience toxicity while still having evidence of clinical benefit and is assessed per the investigator.

Also known as: TMT212, GSK1120212

Main Study

Eligibility Criteria

• Age: 2 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed informed consent and assent (when applicable)
• Males or females age \> 2 months to \< 30 years at the time of informed consent.
• Have a documented Ras/MAPK-pathway variant.
• Have a symptomatic vascular anomaly in need of medical therapy.
• Have a disease-related lesion or lesions which can be measured
• Have a Lansky or Karnofsky performance status score of ≥ 50.
• Have acceptable organ function
• (For persons who can get pregnant) Have a negative serum or urine pregnancy test within 7 days prior to starting study medication.
• Must agree to the use an acceptable method of contraception
• Subjects must be able to swallow tablets or liquid or use a nasogastric or gastric tube

You may not qualify if:

• Subjects seeking treatment for hypertrophic cardiomyopathy without a vascular anomaly
• Prior medications that are not allowable per the study protocol
• Confirmed or possible infections
• History of hepatic sinusoidal obstructive syndrome (veno-occlusive disease of the liver) in the last 3 months.
• Active gastrointestinal (GI) disease
• Subjects with history of or current risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or uncontrolled glaucoma or ocular hypertension.
• Allergic reactions: Subjects with a history of allergic reaction attributed to compounds of similar chemical or biological composition to trametinib are not eligible.
• History of prior and or ongoing cancer or ongoing investigations or treatment for cancer at time of informed consent.
• Subjects unable to comply with safety monitoring requirements.
• Subject may not be pregnant or breast feeding.
• Parents/guardian/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• Debulking or other major surgery performed within 30 days, at time of informed consent;
• Clinically meaningful bleeding related to VA: Grade 2 within 14 days or Grade 3 and more within 28 days before study treatment start as per CTCAE v. 5.0.
• Sclerotherapy/embolization for vascular complications performed within 14 days before informed consent.
• Subjects not able to understand and to comply with study instructions and requirements (in patients, legally authorized representatives, or guardians as applicable) at time of informed consent.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Novartis: collaborator
• CaNVAS (Consortium of Investigators of Vascular Anomalies): collaborator
• Texas Children's: collaborator
• Arkansas Children's Hospital Research Institute: collaborator
• Nationwide Children's Hospital: collaborator
• Nemours Children's Health: collaborator
• Boston Children's Hospital: collaborator
• NYU Langone Health: collaborator
• Children's Healthcare of Atlanta: collaborator
• Oregon Health and Science University: collaborator
• Children's Hospital Colorado: collaborator
• Riley Children's Health: collaborator
• Children's Hospital of Los Angeles (CHLA): collaborator
• Seattle Children's Hospital: collaborator
• Children's Hospital of Orange County (CHOC): collaborator
• Children's Wisconsin - Milwaukee: collaborator
• University of North Carolina: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of California, San Francisco: collaborator
• Children's Hospital of Pittsburg: collaborator
• Dell Children's Medical Center of Central Texas: collaborator
• Vanderbilt University Medical Center: collaborator
• Helen DeVos Children's Hospital: collaborator
• Washington University School of Medicine: collaborator
• Lucile Packard Children's Hospital Stanford: collaborator
• Columbia University Irving Medical Center, New York, NY: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Comprehensive Vascular Anomalies Program (CVAP) at CHOP
• CaNVAS Research Consortium

MeSH Terms

Conditions

Vascular Malformations

Interventions

trametinib

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase II multi-center non-randomized study to assess the safety and efficacy of trametinib with Ras/MAPK pathway driven vascular anomalies.

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: April 24, 2026
• Study Start: August 27, 2025
• Primary Completion (Estimated): August 27, 2029
• Study Completion (Estimated): August 27, 2030
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)