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

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ClinicalTrials.gov Identifier: NCT04406870
Recruitment Status : Not yet recruiting
First Posted : May 29, 2020
Last Update Posted : May 29, 2020
Sponsor:
Information provided by (Responsible Party):
Shanghai Children's Medical Center

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".

Condition or disease Intervention/treatment Phase
Hemangioendothelioma of Liver Drug: Sirolimus Oral Product Drug: propranolol Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Sirolimus in the Treatment for Propranolol-resistant Infantile Hepatic Hemangioendothelioma
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2025


Arm Intervention/treatment
Experimental: Intervention
patients with propranolol-resistant IHHE are given propranolol combined with sirolimus
Drug: Sirolimus Oral Product
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.
Other Names:
  • TORISEL
  • rapamycin

Drug: propranolol
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.
Other Name: xin de an (chinese name means making me comfortable)




Primary Outcome Measures :
  1. Change of tumor size [ Time Frame: 1 month ]
    measuring the tumor size by ultrasound


Secondary Outcome Measures :
  1. Change of PIVKA-II [ Time Frame: 1 month ]
    Using PIVKA-II assay kit (ARCHITECT I2000SR REFURB, Abbott, America).

  2. Change of alpha-1 fetoprotein (AFP) [ Time Frame: 1 month ]
    Using the AFP assay kit (ARCHITECT AFP, Abbott, America).



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Ages Eligible for Study:   1 Month to 36 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04406870


Contacts
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Contact: Song Gu, Doctor +86-18930830716 gusong@shsmu.edu.cn
Contact: Hongxiong Gao, Master +86-15216606578 guyafeihong@163.com

Locations
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China, Shanghai
Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China, 200127
Contact: Song Gu, Doctor         
Sponsors and Collaborators
Shanghai Children's Medical Center
Investigators
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Study Chair: Song Gu, Doctor Shanghai Children's Medical Center
Publications:

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Responsible Party: Shanghai Children's Medical Center
ClinicalTrials.gov Identifier: NCT04406870    
Other Study ID Numbers: PRL-SRL-IHHE
First Posted: May 29, 2020    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Shanghai Children's Medical Center:
propranolol-resistant
sirolimus
infantile hepatic hemangioendothelioma
Additional relevant MeSH terms:
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Hemangioendothelioma
Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Sirolimus
Propranolol
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents