search
Back to results

Sirolimus in the Treatment for Infantile Hepatic Hemangioendothelioma(IEEH) (PRL-SRL-IHHE)

Primary Purpose

Hemangioendothelioma of Liver

Status
Not yet recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Sirolimus Oral Product
propranolol
Sponsored by
Shanghai Children's Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemangioendothelioma of Liver focused on measuring propranolol-resistant, sirolimus, infantile hepatic hemangioendothelioma

Eligibility Criteria

1 Month - 36 Months (Child)All SexesDoes not accept healthy volunteers

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%

Sites / Locations

  • Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention

Arm Description

patients with propranolol-resistant IHHE are given propranolol combined with sirolimus

Outcomes

Primary Outcome Measures

Change of tumor size
measuring the tumor size by ultrasound

Secondary Outcome Measures

Change of PIVKA-II
Using PIVKA-II assay kit (ARCHITECT I2000SR REFURB, Abbott, America).
Change of alpha-1 fetoprotein (AFP)
Using the AFP assay kit (ARCHITECT AFP, Abbott, America).

Full Information

First Posted
May 17, 2020
Last Updated
May 23, 2020
Sponsor
Shanghai Children's Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT04406870
Brief Title
Sirolimus in the Treatment for Infantile Hepatic Hemangioendothelioma(IEEH)
Acronym
PRL-SRL-IHHE
Official Title
Sirolimus in the Treatment for Propranolol-resistant Infantile Hepatic Hemangioendothelioma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2020 (Anticipated)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Children's Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemangioendothelioma of Liver
Keywords
propranolol-resistant, sirolimus, infantile hepatic hemangioendothelioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Recruiting patients with IHHE who have no response to propranolol after 3 months. Then propranolol combined with sirolimus will be given.
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
patients with propranolol-resistant IHHE are given propranolol combined with sirolimus
Intervention Type
Drug
Intervention Name(s)
Sirolimus Oral Product
Other Intervention Name(s)
TORISEL, rapamycin
Intervention Description
Patients with IHHE wil be treated with propranolol (1 mg / kg , twice a day, after meals), and then evaluation will be performed after 3 months (changes of the tumor size measured by ultrasound examination, and changes of tumor volume measured by abdominal enhancement CT).It will be admitted into the group once the tumor volume shrinks <30%.Then propanolol combined with sirolimus will be given. Propranolol will be given at 1mg/kg,twice a day and sirolimus will be given at 0.8mg/m²(body surface area), twice a day. Recording and doing assessment of tumor size, adverse effects as well as complicated symptoms.
Intervention Type
Drug
Intervention Name(s)
propranolol
Other Intervention Name(s)
xin de an (chinese name means making me comfortable)
Intervention Description
Patients with IHHE wil be treated with propranolol (1 mg / kg , twice a day, after meals), and then evaluation will be performed after 3 months (changes of the tumor size measured by ultrasound examination, and changes of tumor volume measured by abdominal enhancement CT).It will be admitted into the group once the tumor volume shrinks <30%.Then propanolol combined with sirolimus will be given. Propranolol will be given at 1mg/kg,twice a day and sirolimus will be given at 0.8mg/m²(body surface area), twice a day. Recording and doing assessment of tumor size, adverse effects as well as complicated symptoms.
Primary Outcome Measure Information:
Title
Change of tumor size
Description
measuring the tumor size by ultrasound
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Change of PIVKA-II
Description
Using PIVKA-II assay kit (ARCHITECT I2000SR REFURB, Abbott, America).
Time Frame
1 month
Title
Change of alpha-1 fetoprotein (AFP)
Description
Using the AFP assay kit (ARCHITECT AFP, Abbott, America).
Time Frame
1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
36 Months
Accepts Healthy Volunteers
No
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%
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Song Gu, Doctor
Phone
+86-18930830716
Email
gusong@shsmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Hongxiong Gao, Master
Phone
+86-15216606578
Email
guyafeihong@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Song Gu, Doctor
Organizational Affiliation
Shanghai Children's Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Song Gu, Doctor

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23327728
Citation
Requena L, Kutzner H. Hemangioendothelioma. Semin Diagn Pathol. 2013 Feb;30(1):29-44. doi: 10.1053/j.semdp.2012.01.003.
Results Reference
background
PubMed Identifier
27468364
Citation
Chatmethakul T, Bhat R, Alkaabi M, Siddiqui A, Peevy K, Zayek M. Infantile Hepatic Hemangioendothelioma: An Uncommon Cause of Persistent Pulmonary Hypertension in a Newborn Infant. AJP Rep. 2016 Jul;6(3):e260-3. doi: 10.1055/s-0036-1585578.
Results Reference
background
PubMed Identifier
12800377
Citation
Chen CC, Kong MS, Yang CP, Hung IJ. Hepatic hemangioendothelioma in children: analysis of thirteen cases. Acta Paediatr Taiwan. 2003 Jan-Feb;44(1):8-13.
Results Reference
background
PubMed Identifier
16286886
Citation
Mehrabi A, Kashfi A, Schemmer P, Sauer P, Encke J, Fonouni H, Friess H, Weitz J, Schmidt J, Buchler MW, Kraus TW. Surgical treatment of primary hepatic epithelioid hemangioendothelioma. Transplantation. 2005 Sep 27;80(1 Suppl):S109-12. doi: 10.1097/01.tp.0000186904.15029.4a.
Results Reference
background
PubMed Identifier
28318668
Citation
Maaloul I, Aloulou H, Hentati Y, Kamoun T, Mnif Z, Hachicha M. Infantile hepatic hemangioendothelioma successfully treated by low dose of propranolol. Presse Med. 2017 Apr;46(4):454-456. doi: 10.1016/j.lpm.2017.01.010. Epub 2017 Mar 15. No abstract available.
Results Reference
background
PubMed Identifier
30047346
Citation
Chaturvedi K, Steinberg JS, Snyder CS. Cost-effectiveness of treating infantile haemangioma with propranolol in an outpatient setting. Cardiol Young. 2018 Oct;28(10):1105-1108. doi: 10.1017/S1047951118000987. Epub 2018 Jul 26.
Results Reference
background
PubMed Identifier
22331019
Citation
Avagyan S, Klein M, Kerkar N, Demattia A, Blei F, Lee S, Rosenberg HK, Arnon R. Propranolol as a first-line treatment for diffuse infantile hepatic hemangioendothelioma. J Pediatr Gastroenterol Nutr. 2013 Mar;56(3):e17-20. doi: 10.1097/MPG.0b013e31824e50b7. No abstract available.
Results Reference
background
PubMed Identifier
28652510
Citation
Ozdemir ZC, Duzenli Kar Y, Sohret NC, Kebapci M, Bor O. Beta blocker and steroid therapy in the treatment of infantile hepatic hemangioendothelioma. Drug Discov Ther. 2017 Jul 31;11(3):161-164. doi: 10.5582/ddt.2017.01025. Epub 2017 Jul 25.
Results Reference
background

Learn more about this trial

Sirolimus in the Treatment for Infantile Hepatic Hemangioendothelioma(IEEH)

We'll reach out to this number within 24 hrs