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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Drug is supplied in 0.5 mg and 2 mg tablets
West China Hospital of Sichuan University
Chengdu, Sichuan, China
The proportion of patients achieving an objective response at month 12
Objective response was defined as ≥20% reduction in lesion volume compared to that at baseline.
Time frame: 12 months
The proportion of patients achieving an objective response at month 6
Objective response was defined as ≥20% reduction in lesion volume compared to that at baseline.
Time frame: 6 months
lesion responses
The primary endpoint was classified as follow: -Complete involution: 100% resolution of the measured lesion volume; -Nearly complete involution was defined as decrease of ≥75% and \<100%; -Partial involution was defined as decrease of ≥20% and \<75%; -No change was defined as \<20% increase and \<20% decrease in the volumes of LM lesions; -Further growth was defined as ≥20% increase in the volume of index compared with the baseline volume measured. Lesion responses were overall lesion response rate and good lesion response rate. Overall lesion response comprised complete, nearly complete and partial involutions. Good lesion response comprised complete and nearly complete involutions.
Time frame: 6 and 12 months
Quality of life (QOL) in patients
Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Infant Scales (\<2 years) or Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Scales (2-18 years) were used.
Time frame: 12 months
Disease sequelae
Disease sequelae were assessed by site investigators at month 12. The site investigators assessed patients' extremity swelling (if any), general physical activity and exercise levels.
Time frame: 12 months
Frequency of adverse events
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Frequency of adverse events (e.g. gastrointestinal disorders, blood and lymphatic system disorders, metabolic disorders or other abnormal laboratory results, skin disorders and general disorders, etc.) collected by investigator and reported by parents. All adverse events were collected and graded according to Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). The causality of the adverse event was determined by the multidisciplinary staff and was classified as definitively not related, probably not related, possibly related, probably related, or definitively related. Any dose reductions, interruptions, or cessations enacted at the discretion of the investigators were recorded.
Time frame: 12 months