Clinical trial NCT04406870: Sirolimus in the Treatment for Infantile Hepatic Hemangioendothelioma(IEEH)
Official title: Sirolimus in the Treatment for Propranolol-resistant Infantile Hepatic Hemangioendothelioma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Hemangioendothelioma of Liver
Keywords: propranolol-resistant
sirolimus
infantile hepatic hemangioendothelioma
Lead sponsor: Shanghai Children's Medical Center
Sponsor class: OTHER
First posted: 2020-05-29
Enrollment: 36
Sex: ALL
Minimum age (years): 1
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Recruiting patients with IHHE who have no response to propranolol after 3 months. Then propranolol combined with sirolimus will be given.
Primary purpose: TREATMENT

Brief summary: Infantile hepatic hemangioendothelioma (IHHE) is an infantile hemangioma involving the liver.Since 2008, propranolol has been used for the treatment of hemangioma, and some researchers have also started to report the use of propranolol for the treatment of infantile hepatic hemangioma in children. Sirolimus can be used in patients with vascular malformations such as hemangiomas. IHHE is also an infantile hemangioma involving the liver,thus sirolimus may paly the role in treatment of IHHE.The clinical trial explores the efficacy of sequential treatment of sirolimus to refractory IHHE patients resistant with propranolol, to improve the therapeutic effect, reduce the side effects of traditional treatment methods (hormones, interferon), and reduce the number of operations and interventions and to provide a clinical basis for the application of the new therapeutics model of IHHE of "propranolol + sequential sirolimus treatment".

Detailed description: According to the World Health Organization(WHO) classification of digestive system tumors in the fourth edition in 2010, infantile hepatic hemangioendothelioma (IHHE) is an infantile hemangioma involving the liver. It is a benign tumor, which can be subgrouped into focal, multifocal, and diffusing in children, as well as combining vascular malformations of the skin, brain, digestive tract and other organs.Since 2008, propranolol has been used for the treatment of hemangioma, and some researchers have also started to report the use of propranolol for the treatment of infantile hepatic hemangioma in children.And more and more clinicians unanimously recommend propranolol as first-line medication for the treatment of IHHE.However, there are few solutions to propranolol-resistant IHHE. Sirolimus is a serine/threonine kinase which plays a pivotal role in cell mortality, angiogenesis and cell growth. Sirolimus can be used in patients with vascular malformations such as hemangiomas. Children with vascular malformations received 0.1mg/kg of sirolimus orally every day and maintained the blood concentration at 8-15ng/ml. The lesions gradually disappear with time going on. Therefore, sirolimus can be used as a second-line medicine for refractory hemangioma and vascular malformation.Interestingly, the investigator's previous study which is retrospective analysis of 30 patients has indicated the effective rate of propranolol alone in treating infantile hepatic endothelial tumor (IHHE) was 57.7%, while that of sequential treatment combined with sirolimus was 84.6%.So, this clinical trial is going to explore the efficacy of sequential treatment of sirolimus to refractory IHHE patients resistant with propranolol,to improve the therapeutic effect,furtherly, reduce the side effects of traditional treatment methods (hormones, interferon), as well as the number of operations and interventions and to provide a clinical guide for the novel therapeutics model of propranolol combined with sirolimus for sequential treatment of infantile hepatic hemangioendothelioma.

Eligibility criteria: Inclusion Criteria:

* Confirmed as IHHE
* Age between 1 month and 36 months
* Receiving propranolol for 3 months but the tumor size shrinks \<30%
* With written informed consent

Exclusion Criteria:

* Confirmed as hepatoblastoma
* Have accepted surgical resection
* Clinical data missing
* Patients with Kasabach-Merritt phenomenon
* Receiving propranolol for 3 months and the tumor size shrinks \>30%

Primary outcomes:
measure: Change of tumor size
timeFrame: 1 month
Secondary outcomes:
measure: Change of PIVKA-II
timeFrame: 1 month
measure: Change of alpha-1 fetoprotein (AFP)
timeFrame: 1 month
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Children's Medical Center
name: Song Gu, Doctor
role: STUDY_CHAIR
References:
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