Recruiting
Phase 2

Trametinib

Sponsor:

Children's Hospital of Philadelphia

Code:

NCT07549646

Conditions

Ras/MAPK Pathway Vascular Anomalies

Vascular Anomalies

Vascular Anomaly

Eligibility Criteria

Sex: All

Age: 0 - 30

Healthy Volunteers: Not accepted

Interventions

Trametinib

Study Details

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

Study ID

NCT07549646

Start date

Aug 27, 2025

Status verified date

Oct, 2026

Completion date

Oct 27, 2030

Anticipated

Primary completion date

Oct 27, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 30

Healthy Volunteers: Not accepted

Inclusion Criteria:

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

Exclusion Criteria:

1. Subjects seeking treatment for hypertrophic cardiomyopathy without a vascular anomaly
2. Prior medications that are not allowable per the study protocol
3. Confirmed or possible infections
4. History of hepatic sinusoidal obstructive syndrome (veno-occlusive disease of the liver) in the last 3 months.
5. Active gastrointestinal (GI) disease
6. Subjects with history of or current risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or uncontrolled glaucoma or ocular hypertension.
7. Allergic reactions: Subjects with a history of allergic reaction attributed to compounds of similar chemical or biological composition to trametinib are not eligible.
8. History of prior and or ongoing cancer or ongoing investigations or treatment for cancer at time of informed consent.
9. Subjects unable to comply with safety monitoring requirements.
10. Subject may not be pregnant or breast feeding.
11. Parents/guardian/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
12. Debulking or other major surgery performed within 30 days, at time of informed consent;
13. 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.
14. 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.

Study Design

Enrollment

45 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Main Study

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.

Interventions

Trametinib

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.

Primary outcome measure

  • Percentage of subjects with a Substantial Response or Intermediate Response to Trametinib using an Individualized Response Criteria [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. ]

Central Contacts and Locations

Central contacts

CVAP Research Team

267-426-9188CVAPResearch@chop.edu

Locations

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

CVAP Research Team

CVAPResearch@chop.edu

Principal Investigator:

Denise M Adams, MD

More Information

Sponsor

Children's Hospital of Philadelphia

Last update posted

Oct 19, 2026

Last verified

Oct, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-20. This information was provided to ClinicalTrials.gov by Children's Hospital of Philadelphia on 2026-10-19. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.