Trametinib Treatment for Complicated Vascular Anomalies

Safety and Efficacy of Trametinib for Complicated Vascular Anomalies: A Multicenter Prospective Study

Complicated vascular anomalies have diverse etiologies and variable clinical manifestations, and no standardized treatment protocol has been established. Since most patients present with diffuse lesions that are difficult to resect surgically, identifying effective therapeutic strategies is of critical importance. This study aims to evaluate the safety and efficacy of systemic trametinib therapy in patients with complicated vascular anomalies.

In recent years, with the widespread application of molecular diagnostic technologies and the growing awareness of complicated vascular anomalies among clinicians, an increasing number of molecular alterations have been identified in these disorders. This progress has brought new hope for patients who previously lacked standardized treatment options. Multiple somatic point mutations have been discovered in complicated vascular anomalies, and case reports have demonstrated significant therapeutic benefits from mutation-based targeted therapies-particularly in patients with NRAS mutations treated with MEK inhibitors. However, to date, there have been no prospective studies evaluating the safety and efficacy of trametinib in pediatric patients with complicated vascular anomalies. Such research is urgently needed to provide robust clinical evidence to guide treatment decisions for this challenging patient population.

Inclusion Criteria:

• -Presenting a complicated vascular anomalies vascular anomalies with the following characteristics:

  1. Male and female;
  2. Between 1 and 18 years of age;
  3. Complicated vascular anomalies vascular anomalies diagnosis was confirmed by local investigators and by consensus of our multidisciplinary vascular anomaly group at the West China Hospital of Sichuan University based on:

Biopsy; Compatible MRI findings; History and clinical features.

Exclusion Criteria:

1. Patients have allergy or contraindication to MEK inhibitor

2. Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;

3. Patients had a history of a major surgery within 2 weeks before enrollment;

4. Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;

5. Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of trametinib.

6. Concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).

7. Patients with inadequate liver function:

   Total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age.

8. Patients with inadequate renal function:

   0-5 years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-14 years of age maximum serum creatinine (mg/dL) of 1.2;

9. Adequate bone marrow function:

   Absolute neutrophil count lower than 1 × 109/L;

10. History of a malignancy within 5 years;

11. HIV infection or known immunodeficiency;

12. Patients with an inability to participate in or follow-up during the study treatment and assessment plan;

13. Inability to give informed consent.