None listed
Conditions
Brief summary
Why is this study important? Vascular anomalies comprise a diverse group of diagnoses. The majority of these conditions are quite rare and have not been widely studied. Some of these lesions can impair vital structures, be deforming or even becoming life-threatening. Many children with complicated vascular anomalies have already failed the conventional treatment and are at risk of significant morbidity and mortality. Currently sirolimus is in clinical trials in various centres of Europe and United States of America. Case studies are suggestive of optimistic outcome. By doing this prospective study, we will be able to assess the response and safety of this medication in our own patients which will definitely be a valuable contribution to the wider medical world to shine light on the management of this rare complex conditions . The protocol is designed as a prospective research study. It involves children in the age group of Zero to Eighteen years. We envisage approximately 6 children per year for 5 years who have complex vascular anomalies will be deemed eligible for treatment with sirolimus. This includes children who are ineligible for or refractory to conventional treatments as well as children who are suffering from rare subtypes of vascular anomaly for whom there is no universally accepted standard therapy. BACKGROUND INFORMATION Vascular anomalies include a heterogeneous group of disorders that are categorized as vascular tumors or vascular malformations. The standard treatment options include resection, sclerotherapy and cytostatic chemotherapy. Some of these anomalies can be very complicated causing disfigurement, chronic pain and organ dysfunction with significant morbidity and mortality. These complicated vascular anomalies are quite rare and have not been widely studied. These patients have either failed the conventional treatment or unable to tolerate the available treatment due to life threatening side effects. 4 Supporting References from the review of literature 1) Adrienne M, MarySue W etal. Sirolimus for the treatment of complicated vascular anomalies in children. Paediatr Blood Cancer 2011;57:1018-1024. 2) Denise M, Cameron C etal. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics2016Feb 18:137(2):1-10. 3) Lackner H, Karastaneva A etal. Sirolimus for the treatment of children with various complicated vascular anomalies. Eur J Pediatr 2015 Dec; 174(12):1579-84. 4) Laurence M, Jennifer H etal. Rapamycin as novel treatment for refractory to standard care venous malformation. ISSVA 2016 Conference abst
Interventions
Treatment with sirolmus ( dose of sirolimus will be calculated based on the surface area of the child (0.8mg/m2/dose twice daily). Its an orally administered medication. Pre-treatment blood and relevant imaging tests will be conducted. Blood levels of sirolimus will be monitored along with other blood tests at regular intervals. Target sirolimus level s will be 10-15 micrograms/litre. The duration of treatment with sirolimus will be 12 months. Sirolimus is an immune modulator so there is a risk
Treatment with sirolmus ( dose of sirolimus will be calculated based on the surface area of the child (0.8mg/m2/dose twice daily). Its an orally administered medication. Pre-treatment blood and relevant imaging tests will be conducted. Blood levels of sirolimus will be monitored along with other blood tests at regular intervals. Target sirolimus level s will be 10-15 micrograms/litre. The duration of treatment with sirolimus will be 12 months. Sirolimus is an immune modulator so there is a risk of Pneumocystis Carinii pneumonia so prophylaxis in the form of co-trimoxazole (Bactrim) 2.5mg/kg/dose, administered orally in the form of tablet or suspension twice daily three times a week on Mondays, Wednesdays and Fridays will be prescribed for all the patients while on sirolimus (12 months or as long as they are on sirolimus). Educating children and parents related to the importance of adherence prior to commencement of sirolimus and frequent follow up /blood sirolimus monitoring at regular intervals to ensure complianace.
Sponsors
Sydney Children's Hospital, Randwick
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Days to 18 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria include children in the age group of zero to eighteen years who have complex vascular anomalies. Examples include children with the following: 1. Venous Malformations with localised intravascular coagulopathy or severe pain failing to respond to sclerotherapy and /or surgery; 2. Lymphatic Malformations which compromise the airway or vision or are causing a low albumin level; 3. Newly diagnosed Kaposiform haemangioendothelioma/tufted angioma: in view of the promising data from the US on the use of sirolimus as initial treatment for KHE (1,2,5), sirolimus will be given to newly diagnosed patients and the results compared to our historical controls, namely children who had received vincristine as initial therapy. 4. Relapsed Kaposiform haemangioendothelioma: children who have previously been successfully treated with vincristine therapy and then have a recurrence of their tumour will be treated with sirolimus; 5. Generalised Lymphatic Anomalies with bone erosions, chylous leak or infiltration of lungs and gastrointestinal tract; 6. localised lymphatic anomalies not amenable to an operation; 7. Children with various overgrowth syndromes who have benign tumours, asymmetry, pain and coagulopathy that have failed usual therapeutic options and are causing significant symptoms
Exclusion criteria
Children who are severely immunocompromised will be excluded from the study.
Outcome results
None listed