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

May 23, 2020 updated by: Shanghai Children's Medical Center

Sirolimus in the Treatment for Propranolol-resistant Infantile Hepatic Hemangioendothelioma

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".

Study Overview

Status

Not yet recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200127
        • Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine
        • Contact:
          • Song Gu, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 3 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • rapamycin
  • TORISEL
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 Names:
  • xin de an (chinese name means making me comfortable)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of tumor size
Time Frame: 1 month
measuring the tumor size by ultrasound
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of PIVKA-II
Time Frame: 1 month
Using PIVKA-II assay kit (ARCHITECT I2000SR REFURB, Abbott, America).
1 month
Change of alpha-1 fetoprotein (AFP)
Time Frame: 1 month
Using the AFP assay kit (ARCHITECT AFP, Abbott, America).
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Children's Medical Center

Investigators

  • Study Chair: Song Gu, Doctor, Shanghai Children's Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2020

Primary Completion (Anticipated)

June 30, 2024

Study Completion (Anticipated)

June 30, 2025

Study Registration Dates

First Submitted

May 17, 2020

First Submitted That Met QC Criteria

May 23, 2020

First Posted (Actual)

May 29, 2020

Study Record Updates

Last Update Posted (Actual)

May 29, 2020

Last Update Submitted That Met QC Criteria

May 23, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRL-SRL-IHHE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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