Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma

Study Overview
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Brief Summary
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to evaluate the safety and efficacy of Low-dose sirolimus in Kaposiform Hemangioendothelioma in Chinese children by a prospective, randomized open trial.

Detailed Description
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The clinically commonly used dose of sirolimus for Kaposiform Hemangioendothelioma is 0.8 mg/m2 administered twice daily, and the blood concentration can be maintained at 10-15 ng/ml according to the pharmacokinetic formula.Related research reports that maintaining low blood concentration of sirolimus is effective in the treatment of certain vascular malformations and hemangioma, and complications are less. In the clinical practice, we found that the blood concentration was maintained at 7-10 ng/ml, and the patients still achieved good results and the chance of infections decreased. Therefore, this clinical trial was designed.In this trial, two different dosing regimens with corresponding blood concentration were designed to compare the safety and efficacy.In the high concentration group, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL(excluding 10 ng/ml), and it is still used at 0.8 mg/m2 administered twice daily.The low concentration group is 7-10 ng/ml (including 10 ng/ml), and the initial use of sirolimus is 0.7mg/m2 administered twice daily.The dose was adjusted according to the formula after two weeks.The follow-up and evaluation were performed according to a strictly established follow-up schedule after taking the drug.

Official Title
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Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma:A Prospective, Randomized Open Trial

Conditions
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Hemangioma, Kaposiform Hemangioendothelioma

Intervention / Treatment
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* Drug: Sirolimus(0.8mg/m2)
* Drug: Sirolimus(0.7mg/m2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kaposiform Hemangioendotheliomas with or without Kasabach-Merritt Phenomenon. 0 - 12 years of age at the time of study entry. Male or female. Consent of parents (or the person having parental authority in families): Signed and dated written informed consent. Exclusion Criteria: with hematological diseases. with other solid tumors. with hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency. with tuberculosis,cytomegalovirus and Epstein-Barr virus infection before the treatment.

Ages Eligible for Study
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Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: high blood concentration group<br>The blood concentration is maintained at 10-15ng/ml (not including 10ng/ml). | Drug: Sirolimus(0.8mg/m2)<br>* The initial use of sirolimus is 0.8mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.<br>* Other names: Rapamycin;|
| Experimental: low blood concentration group<br>The blood concentration is maintained at 7-10ng/ml (including 10ng/ml). | Drug: Sirolimus(0.7mg/m2)<br>* The initial use of sirolimus is 0.7mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.<br>* Other names: Rapamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response to treatment | it is a variable outcome, including complete responses, partial response and no response. The definitions are : Complete Response： platelets counts is greater than 100×10^9/L. significant volume reduction is greater than 80%. Fibrinogen levels at 2-4g/L. The surface skin of the tumor is lighter or the tumor is softer significantly. Partial Response: platelets counts is greater than 40×10^9/L. significant volume reduction is greater than 50%. Fibrinogen levels at less than 50% reduction from baseline. The surface skin of the tumor and palpation of the tumor have no change or less change. No Response: platelets counts is less than 40×10^9/L. significant volume reduction is less than 50% or the tumor is bigger. Fibrinogen levels at grater then 50% reduction from baseline. The surface skin of the tumor is darker or the tumor is harder. | 1 year after taking the drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Monitoring patient's clinical biochemical indicators and symptoms | 1 year after taking the drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kaposiform Hemangioendothelioma, Kasabach-Merritt Syndrome, Sirolimus, Rapamycin