Vascular Anomalies
Conditions
Keywords
complicated vascular anomalies
Brief summary
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.
Detailed description
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.
Interventions
Drug is supplied in 0.5 mg and 2 mg tablets
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients achieving an objective response at month 12 | 12 months | Objective response was defined as ≥20% reduction in lesion volume compared to that at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients achieving an objective response at month 6 | 6 months | Objective response was defined as ≥20% reduction in lesion volume compared to that at baseline. |
| lesion responses | 6 and 12 months | 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. |
| Quality of life (QOL) in patients | 12 months | 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. |
| Disease sequelae | 12 months | 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. |
| Frequency of adverse events | 12 months | 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. |
Countries
China
Outcome results
None listed