Kaposiform hemangioendothelioma or Tufted angioma Lymphangioma (cystic lymphatic malformation), lymphangiomatosis (generalized lymphatic anomaly) or Gorham-Stout disease Venous malformation or blue rubber bleb nevus syndrome Complex-combined vascular malformations or Klippel-Trenanay-Weber syndrome
Conditions
Interventions
An initial dose of sirolimus is single orally administered under fed or fasting condition. Subsequently, the sirolimus dosage is adjusted to achieve trough levels between 5-15 ng/mL.
Sponsors
Gifu University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Corrected aged 1 month or more at consent 2) Patients definitively diagnosed with the following diseases. Kaposiform hemangioendothelioma or Tufted angioma Lymphangioma (cystic lymphatic malformation), lymphangiomatosis (generalized lymphatic anomaly) or Gorham-Stout disease Venous malformation or blue rubber bleb nevus syndrome Complex-combined vascular malformations or Klippel-Trenanay-Weber syndrome 3) Patients having one or more measurable lesions evaluated by pretreatment MR imaging 4) Patients must have vascular anomalies that have potential to cause significant morbidity. 5) Normal liver, renal, and cardiac function at entry Total bilirubin < 3 x ULN for age CRE < 3 x ULN for age 6) Written consent to participate in this clinical trial has been given by the subject in person or by a legal guardian (when the subject is younger than 20 years at consent).
Exclusion criteria
Exclusion criteria: 1) Past usage of mTOR inhibitors excluding sirolimus or other molecular target drugs relating mTOR pathway within 8 weeks 2) Patients who currently have an uncontrolled infection 3) Karnofsky Performance Status (PS) <= 30 (10 years of age) or Lansky play PS <= 30 (< 10 years of age) 4) Interstitial lung disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, chronic liver disease, or chronic renal disease 5) Chronic treatment (>= 4 weeks) with systemic steroids or another immunosuppressive agent at entry. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. 6) History of allergy to sirolimus, or additive substance 7) Patients must also avoid strong inducers of CYP3A4, and may not have received these medications within 1 week of entry. 8) Known history of HIV seropositivity or known immunodeficiency 9) Hepatitis B virus carrier and/or Hepatitis C virus carrier 10) Malabsorption of sirolimus 11) Patients who have undergone surgical resection or interventional radiology procedures for target lesions within 2 weeks 12) Patients who have received therapeutic medication for a target disease within 2 weeks 13) Patients who have received chemotherapy drugs that cause bone marrow suppression, biological drug, or off-label products within 4 weeks 14) Patients who have received radiation therapy for target lesions within 24 weeks 15) Patients who have participated another clinical trial within 4 weeks 16) Patients who have dental braces or prosthesis only if it interferes with radiologic analysis of lymphatic anomaly 17) Pregnant, probably pregnant, or breast-feeding woman. Patients or their partners who do not agree birth control during clinical trial. 18) Patients who have participated in clinical trial of sirolimus in the past. 19) Patient who is judged inappropriate to participate in this study by the investigators
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Target lesion response rate determined by Independent Review Facility after 24 weeks of treatments | — |
Secondary
| Measure | Time frame |
|---|---|
| Target lesion response rate determined by Independent Review Facility after 12 and 52 weeks of treatments Improvement of Skin lesion after 12, 24 and 52 weeks of treatments Evaluation of pleural effusion after 12, 24 and 52 weeks of treatments Evaluation of ascites after 12, 24 and 52 weeks of treatments Blood coagulation parameters after 12, 24 and 52 weeks of treatments Bleeding after 12, 24 and 52 weeks of treatments Pain after 12, 24 and 52 weeks of treatments QOL improvement rates after 12, 24 and 52 weeks of treatments ADL improvement rates after 12, 24 and 52 weeks of treatments Adverse events and side effects Laboratory values Vital signs Pharmacokinetics | — |
Countries
Japan
Contacts
Public ContactMichio Ozeki
Gifu University Hospital Pediatrics
Outcome results
None listed