efficacy and safety of sirolimus to vascular anomalies

Conditions: Vascular Anomaly

Summary: to evaluate the safety and efficacy of sirolimus in complicated vascular anomalies in chinese children

vascular anomalies are composed of vascular tumors and vascular malformations. the prognosis of vascular anomalies is significantly variable. most of them had a benign course. however, complicated vascular anomalies can lead to disfigurement, organ disfunction and life-threatening with significant morbidity and mortality. traditional treatments, including steroids, vincristine, cyclophosphamide and surgery, had limited response to complicated vascular anomalies. in the past few years, the inhibitor of the mammalian target of rapamycin (mtor) signaling pathway-sirolimus has emerged as a treatment for severe vascular anomalies. besides, preclinical studies also showed that the phosphoinositide 3-kinase (pi3k)/protein kinase b (akt)/mtor pathway play an important role in the development of vascular tumors and vascular malformations. however, the exact efficacious rate and complications of sirolimus are still unknow in china because of the lack of large scale of prospective studies. therefore, it's important to perform this prospective study to determine the safety and efficacy of sirolimus in the treatment of chinese children with complicated vascular anomalies, and this study will also make contributions to the diagnoses and treatments of vascular anomalies.

Eligibility criteria:
inclusion criteria: * all patients included in the present research must be diagnosed with one of the following vascular anomalies: 1. kaposiform hemangioendotheliomas without kasabach-merritt phenomenon 2. tufted angioma without kasabach-merritt phenomenon 3. capillary malformations 4. lymphatic malformations 5. venous malformations 6. capillary-venous malformation (cvm) 7. capillary-lymphatic malformation (clm) 8. lymphatic-venous malformation (lvm) 9. capillary-lymphatic-venous malformation (clvm) 10. multifocal lymphangiomatosis and thrombocytopenia (mlt) * patients must be 0 - 18 years of age at the time of study entry. * without functional impairment requiring treatment of corticosteroid. * organ function requirements: * adequate liver function total bilirubin less than or equal to 1.5 x upper limit of normal (uln)for age, and alanine transaminase (alt) and aspartate aminotransferase (ast) less than or equal to 2.5 x upper limit normal (uln) for age. * adequate 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 11-15 years of age maximum serum creatinine (mg/dl) of 1.2 16-18 years of age maximum serum creatinine (mg/dl) of 1.5 * adequate bone marrow function: absolute neutrophil count (anc) greater than or equal to 1 x 10 to the ninth/liter * consent of parents (or the person having parental authority in families): signed and dated written informed consent. exclusion criteria: * allergy to sirolimus or other rapamycin analogues. * allergy to sirolimus or other rapamycin analogues. * any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization. * patients must not be known to be human immunodeficiency virus positive or known immunodeficiency. testing is not required unless a condition is suspected. * other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration). * impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus. * patients who have a history of malignancy. * patients with an inability to participate or to follow the study treatment and assessment plan. * patients who have a history of treatment with sirolimus or other mtor inhibitor.

Keywords: sirolimus vascular anomalies