Description:
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".
Title
- Brief Title: Sirolimus in the Treatment for Infantile Hepatic Hemangioendothelioma(IEEH)
- Official Title: Sirolimus in the Treatment for Propranolol-resistant Infantile Hepatic Hemangioendothelioma
Clinical Trial IDs
- ORG STUDY ID:
PRL-SRL-IHHE
- NCT ID:
NCT04406870
Conditions
- Hemangioendothelioma of Liver
Interventions
| Drug | Synonyms | Arms |
|---|
| Sirolimus Oral Product | TORISEL, rapamycin | Intervention |
| propranolol | xin de an (chinese name means making me comfortable) | Intervention |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Intervention | Experimental | patients with propranolol-resistant IHHE are given propranolol combined with sirolimus | - Sirolimus Oral Product
- propranolol
|
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%
| Maximum Eligible Age: | 36 Months |
| Minimum Eligible Age: | 1 Month |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Change of tumor size |
| Time Frame: | 1 month |
| Safety Issue: | |
| Description: | measuring the tumor size by ultrasound |
Secondary Outcome Measures
| Measure: | Change of PIVKA-II |
| Time Frame: | 1 month |
| Safety Issue: | |
| Description: | Using PIVKA-II assay kit (ARCHITECT I2000SR REFURB, Abbott, America). |
| Measure: | Change of alpha-1 fetoprotein (AFP) |
| Time Frame: | 1 month |
| Safety Issue: | |
| Description: | Using the AFP assay kit (ARCHITECT AFP, Abbott, America). |
Details
| Phase: | Phase 4 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Shanghai Children's Medical Center |
Trial Keywords
- propranolol-resistant
- sirolimus
- infantile hepatic hemangioendothelioma
Last Updated
May 29, 2020
