Vascular Anomalies Clinical Trial
Official title:
A Phase II Clinical Study to Evaluate the Efficacy and Safety of Rapamycin in Complex Vascular Anomalies in Pediatric Patients
KHE and TA are rare tumors and some of the cases may lead to life-threatening complications including Kasabach-Merritt Phenomenon. Typically treated with steroids and vincristine, a majority of the cases do not have good prognosis. Complex vascular malformations are always managed by surgery,sclerotherapy and embolization therapy. While many of the cases still lead to complications such as disfigurement, chronic pain, recurrent infections, coagulopathies. Different medical centers are exploring new therapy for these tough problems. This study is plotted to determine the efficacy and safety of rapamycin monotherapy in KHE/TA and complex vascular malformations in pediatric patients.
According to the classification （revised in 2014）by International Society for the Study of Vascular （ISSVA ）, vascular anomalies are classified into two distinct disease entities，including vascular tumors and vascular malformations differing in their biologic and pathologic features. Vascular tumors include infantile and congenital hemangiomas, Tufted angiomas (TA), and Kaposiform hemangioendotheliomas (KHE). Vascular malformations are classified according to their vascular tissue of origin which include capillary, venous, arteriovenous, lymphatic, and mixed malformations. Infantile hemangiomas, the most common vascular anomaly, generally have a good prognosis due to its specific biological characteristics（a predetermined life cycle from proliferation to subsequent involution). However，KHE and TA are rare vascular tumors with incidence less than 1/1000000 and along with complex lymphatic malformations and complex mixed malformations，are difficult to be successfully treated resulting in clinical problems such as disfigurement, chronic pain, recurrent infections, coagulopathies (thrombotic and hemorrhagic,including life-threatening Kasabach-Merritt Phenomenon), organ dysfunction. Rapamycin directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and angio/lymphangiogenesis and is recently applied to refractory vascular . Preclinical data and case reports have confirm that rapamycin is effective for KHE/TA and some slow-flow vascular malformations. The overall goal of this trial is to objectively determine the effectiveness and safety of rapamycin monotherapy in KHE/TA and complex vascular malformations in pediatric patients and to explore the rational doses. In this study, 30 patients (aged from 1 month to 14 years old) diagnosed with KHE/TA or complex vascular that respond poorly to propranolol hydrochloride and corticosteroid are enrolled. Oral rapamycin is given as a monotherapy at a initial dose of 0.8mg/m2, once daily for children under 3 years old and twice daily (every 12 hours) for those above 3 years. And further dosage is adjusted to target a trough concentration of rapamycin in plasma as 10-15ng/ml （OR 15-20ng/ml if the efficacy of treatment is not satisfactory with concentration at 10-15ng/ml. One course lasts for 12weeks and no more than 4 courses are given.Volumetric changes as the primary outcome measure will be analysed by magnetic resonance imaging (MRI) and/or ultrasonography. Frequency of adverse events as assessed by CTCAE v4.0 is calculated to evaluate the safety of rapamycin. ;
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