Sirolimus in the Treatment for Infantile Hepatic Hemangioendothelioma(IEEH)

NCT04406870 | Unknown Phase 4 DMC

• 1 other identifier: PRL-SRL-IHHE
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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".

Conditions

Hemangioendothelioma of Liver

Keywords

propranolol-resistant; sirolimus; infantile hepatic hemangioendothelioma

Outcome Measures

Primary Outcomes (1)

• Change of tumor size

  measuring the tumor size by ultrasound

  1 month

Secondary Outcomes (2)

• Change of PIVKA-II

  1 month

• Change of alpha-1 fetoprotein (AFP)

  1 month

Study Arms (1)

Intervention

EXPERIMENTAL

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

Drug: Sirolimus Oral Product; Drug: propranolol

Interventions

Sirolimus Oral Product DRUG

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.

Also known as: TORISEL, rapamycin

Intervention

propranolol DRUG

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.

Also known as: xin de an (chinese name means making me comfortable)

Intervention

Eligibility Criteria

• Age: 1 Month - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Shanghai Children's Medical Center: lead

Study Sites (1)

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

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (8)

• Requena L, Kutzner H. Hemangioendothelioma. Semin Diagn Pathol. 2013 Feb;30(1):29-44. doi: 10.1053/j.semdp.2012.01.003.

  PMID: 23327728 BACKGROUND

• 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.

  PMID: 27468364 BACKGROUND

• 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.

  PMID: 12800377 BACKGROUND

• 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.

  PMID: 16286886 BACKGROUND

• 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.

  PMID: 28318668 BACKGROUND

• 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.

  PMID: 30047346 BACKGROUND

• 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.

  PMID: 22331019 BACKGROUND

• 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.

  PMID: 28652510 BACKGROUND

MeSH Terms

Interventions

temsirolimus; Sirolimus; Propranolol

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Song Gu, Doctor

  Shanghai Children's Medical Center

  STUDY CHAIR

Central Study Contacts

Song Gu, Doctor

CONTACT

+86-18930830716; gusong@shsmu.edu.cn

Hongxiong Gao, Master

CONTACT

+86-15216606578; guyafeihong@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Recruiting patients with IHHE who have no response to propranolol after 3 months. Then propranolol combined with sirolimus will be given.

Study Record Dates

• First Submitted: May 17, 2020
• First Posted: May 29, 2020
• Study Start: July 1, 2020
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2025
• Last Updated: May 29, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)