Systematic Approach for Children With Orbital Malformation With Sirolimus Use (sirolimus)

January 23, 2026 updated by: nihal hussien aly, Ain Shams University

Systematic Management Approach for Children and Adolescents With Orbital Lymphatic Malformation

The goal of this interventional study is to Set a systematic management approach for orbital lymphatic malformation and to study the safety and efficacy of sirolimus in children and adolescents with orbital lymphatic malformation]. The main questions it aims to answer are:

[what is the safety of using sirolimus in patients with orbital lymphatic malformation]? [what is the efficacy of sirolimus in patients with orbital lymphatic malformation]? Participants will be divided into three groups based on their symptoms, extent and type of orbital lymphatic malformation Group 1 ( will receive injection sclerotherapy): All Patients with symptomatic lymphatic malformation except those with complex malformation , Group 2 (will receive sirolimus on 0.8 mg per m2 twice daily for 6 months ):A) Patients with symptomatic complex lymphatic malformation.

B) Patients in group 1 if there is progression in lesion size or ineffective local therapy Group 3 ( will receive both injection sclerotherapy and sirolimus):A) Patients in group 1 and patients with complex lymphatic malformation if there is concern for complications like hemorrhage, amblyopia and vision loss since diagnosis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an interventional study aiming at setting systematic approach for children and adolescents with orbital lymphatic malformation and to assess the safety and efficacy of sirolimus in patients with orbital lymphatic malformation Patients with lymphatic malformation will be subdivided according 4 grades, grade1 the size of the cyst, grade 2 the extension , grade 3 the angiogensis , grade 4 according to symptoms Grade 1:According to the size of cyst, Lymphatic malformation are divided into macrocystic (>2cm), microcystic(<2cm) and mixed cyst.Grade 2: According to the extension , lymphatic malformation are divided into superficial (presenting as a subcutaneous cyst); deep (having orbital infiltration);combined (superficial and deep components); complex (intracranial or head and neck infiltration) (10).

Grade 3: According to angiogensis, lymphatic malformation are divided into simple lympahtic malformation or combined with venous element or capillary malformation Grade 4 : According to symptoms , lymphatic malformation are divided into asympyomatic and symptomatic Patients will be assigned to available treatment modality either local control via injection sclerotherapy or surgery verus sirolimus orally either alone or combined with local control.

Group 1: All Patients with symptomatic lymphatic malformation except those with complex lymphatic malformation.They will be assigned to sclerotherpay .Local intralesional trancutaneous injection dose will be 0.6 mg / kg of bleomycin dissolved in the total volume of the lesion calculated from dimensions of orbital lesion in MRI orbit with contrast. Intralesional injection frequency will be guided by clinical response of the patients and imaging studies.If there is response clinically, injection will be continued every one month until there is no further response or if the lesion is reaching 75% of lesion size Or if there is no response from first injection.For lid and conjunctival components local injection will be for small , moderate and large lesions 2 IU, 4 IU, 6 IU respectively and further injection every month guided by lesion response.Less than 25% reduction will not receive further injection, if there is 25%- 50 % reduction injection will continue till reaching 75% or more clinical reduction in size (9) Group 2: Patients assigned to sirolimus arm will be patients with A) Patients with symptomatic complex lymphatic malformation. B) Patients in group 1 if there is progression in lesion size or ineffective local therapy.

Group 3 :Patients assigned to both modality from the start :

A) Patients in group 1 or complex if there is concern for complications like hemorrhage, amblyopia and vision loss since diagnosis.

Dose will be 0.8 mg/m2 twice daily orally for 6 months ,published literature for sirolimus' use in the pediatric population recommends a starting dose of sirolimus 1.6 mg/m2/day divided twice daily (10) with target trough level of 8-15 ng/ml will be done after 2 weeks from starting therapy , available containing tablets are rapimmune tablets (1 mg), tablets should not be crushed nor chew, or spilted, it should be taken in the same way either with food or without.Grapefruit juice reduces CYP3A4-mediated drug metabolism. Grapefruit juice must not be taken with or used for dilution of Rapamune .Immunosuppressants may affect response to vaccination.During treatment with sirolimus, vaccination may be less effective. The use of live vaccines should be avoided; live vaccines may include, but are not limited to, the following: measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid

All patients will be subjected to the detailed history with data at diagnosis collected from the filing system

  1. Detailed medical history with special emphasis on:Demographic data , the presenting symptoms, the course of the disease, any complications like proptosis , pain , bleeding or cosmetic disfigurement.Treatment that will be received including sclerotherapy ( type of sclerosant agent, frequency, dose and response assessment), drug therapy (sirolimus including dose , drug level, side effects and response assessment)

  2. Thorough clinical examination laying stress on:

    Physical examination for the site , the size , the colour, the consistency , the tenderness, systemic examination for associated anomalies was done. Blood pressure measurement for patients on siroloimus at each visit.

  3. Laboratory investigations:

Complete blood count (CBC) before intervention and after 2 weeks from starting sirolimus then every 3 months while the patient is receiving it. Sirolomus level for patients who are assigned to sirolimus after 2 weeks from starting therapy and in case of progression or development of reported side effect.

Alanine transaminase , serum creatinine, lipid profile including (cholesterol and triglycerides) after 3 months and after 6 months from start of treatment in patient group on sirolimus.

1- Radiological assessment:

1- MRI orbit and brain vascular anomaly protocol (conventional pre contrast MRI and dynamic post contrast sequences) to confirm diagnosis, and detect extension for deeper lesion and after 6 months of intervention to assess radiological improvement.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Egypt
    • Cairo Governorate
      • Cairo, Cairo Governorate, Egypt, 11321
        • Recruiting
        • Ain Shams University
        • Contact:
        • Contact:
        • Sub-Investigator:
          • iman ahmed ragab, MD
        • Sub-Investigator:
          • azza mohamed ahmed, MD of ophthalmology
        • Sub-Investigator:
          • amr zaky abuzeid, MD of pediatric surgery
        • Sub-Investigator:
          • shimaa mohamed abdel sattar, MD of radiology
        • Principal Investigator:
          • nihal hussien Mostafa

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Age : 1-18 years Children and adolescents diagnosed with orbital low flow vascular malformation based on clinical , radilogical findings

Exclusion Criteria:

Children and adolescents with orbital high flow vascular malformation

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Group 1: All Patients with symptomatic LM except complex type
Group 1: All Patients with symptomatic lymphatic malformation except those with complex lymphatic malformation.They will be assigned to sclerotherpay .Local intralesional trancutaneous injection dose will be 0.6 mg / kg of bleomycin dissolved in the total volume of the lesion calculated from dimensions of orbital lesion in MRI orbit with contrast. Intralesional injection frequency will be guided by clinical response of the patients and imaging studies.If there is response clinically, injection will be continued every one month until there is no further response or if the lesion is reaching 75% of lesion size Or if there is no response from first injection.For lid and conjunctival components local injection will be for small , moderate and large lesions 2 IU, 4 IU, 6 IU respectively and further injection every month guided by lesion response.Less than 25% reduction will not receive further injection, if there is 25%- 50 % reduction injection will continue till reaching 75%
Procedure: Injection Sclerotherapy
For group 1: They will be assigned to sclerotherpay .Local intralesional trancutaneous injection dose will be 0.6 mg / kg of bleomycin dissolved in the total volume of the lesion calculated from dimensions of orbital lesion in MRI orbit with contrast. Intralesional injection frequency will be guided by clinical response of the patients and imaging studies.If there is response clinically, injection will be continued every one month until there is no further response or if the lesion is reaching 75% of lesion size Or if there is no response from first injection.For lid and conjunctival components local injection will be for small , moderate and large lesions 2 IU, 4 IU, 6 IU respectively and further injection every month guided by lesion response.Less than 25% reduction will not receive further injection, if there is 25%- 50 % reduction injection will continue till reaching 75% or more clinical reduction in size
Active Comparator: Group 2: Patients with complex LM or patients from group 1 if no response

Patients assigned to sirolimus arm will be patients with A) Patients with symptomatic complex lymphatic malformation. B) Patients in group 1 if there is progression in lesion size or ineffective local therapy.

Dose will be 0.8 mg/m2 twice daily orally for 6 months ,published literature for sirolimus' use in the pediatric population recommends a starting dose of sirolimus 1.6 mg/m2/day divided twice daily (10) with target trough level of 8-15 ng/ml will be done after 2 weeks from starting therapy
Drug: Sirolimus (Rapamune®)
Dose will be 0.8 mg/m2 twice daily orally for 6 months ,published literature for sirolimus' use in the pediatric population recommends a starting dose of sirolimus 1.6 mg/m2/day divided twice daily (10) with target trough level of 8-15 ng/ml will be done after 2 weeks from starting therapy
Active Comparator: Group 3: A) Patients in group 1 or complex if there is concern for complications like hemorrhage, am
Dose will be 0.8 mg/m2 twice daily orally for 6 months ,published literature for sirolimus' use in the pediatric population recommends a starting dose of sirolimus 1.6 mg/m2/day divided twice daily (10) with target trough level of 8-15 ng/ml will be done after 2 weeks from starting therapy
Other: both injection sclerotherapy and sirolimus
They will be assigned to sclerotherpay .Local intralesional trancutaneous injection dose will be 0.6 mg / kg of bleomycin dissolved in the total volume of the lesion calculated from dimensions of orbital lesion in MRI orbit with contrast. Intralesional injection frequency will be guided by clinical response of the patients and imaging studies.If there is response clinically, injection will be continued every one month until there is no further response or if the lesion is reaching 75% of lesion size Or if there is no response from first injection.For lid and conjunctival components local injection will be for small , moderate and large lesions 2 IU, 4 IU, 6 IU respectively and further injection every month guided by lesion response.Less than 25% reduction will not receive further injection, if there is 25%- 50 % reduction injection will continue till reaching 75% or more clinical reduction in size sirolimus will be given in a dose of 0.8 mg per m2 twice daily .

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
safety of sirolimus in patients with orbital lymphatic malformation
Time Frame: 6 months
assessment of safety of sirolimus
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
efficacy of sirolimus in patients with orbital malformation
Time Frame: 6 months
reduction size of the lymphatic malformation and recovery of symptoms
6 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ain Shams University

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 23, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 30, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FMASU R 271/2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

data will be available upon request

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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