Efficacy and Safety of Different Concentrations of Sirolimus in the Treatment of Kaposiform Hemangioendothelioma.

May 5, 2024 updated by: Yi Ji, West China Hospital

Efficacy and Safety of High- vs Low-Dose Sirolimus in Patients With Kaposiform Hemangioendothelioma: A Trial Protocol

The purpose of this study is to compare the efficacy and safety of different concentration gradients of sirolimus in the treatment of Kaposiform hemangioendothelioma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular neoplasm that occurs predominantly in infancy or early childhood, with an incidence of approximately 0.71/100,000. Currently, sirolimus is a promising treatment modality for KHE. Most scholars consider sirolimus blood concentration of 5-15 ng/ml to be an effective therapeutic concentration.

However, long-term higher dose sirolimus treatment can cause some common complications such as oral mucositis which affects the quality of life of the patient. Finer control of the plasma concentration of sirolimus may contribute to the efficacy of treatment and reduce the incidence of complications. Therefore, we conducted this study to see if low-dose sirolimus is beneficial to the prognosis of patients.

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China Hospital of Sichuan University

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 day to 18 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Presenting a KHE with the following characteristics:

  1. Male and female;
  2. Between 0 and 14 years of age;

  3. KHE diagnosis was confirmed by local investigators and by consensus of our multidisciplinary vascular anomaly group at the West China Hospital of Sichuan University based on:

    • Biopsy;
    • Compatible MRI findings;
    • History and clinical features.

    The multidisciplinary vascular anomaly group was a collaboration team that included vascular anomaly experts in pediatric surgery, plastic surgery, pediatric dermatology, pathology and radiology.

  4. Without KMP, which was defined as a platelet count of less than 100×10^9/L, with consumptive coagulopathy and hypofibrinogenemia.
  5. Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
  6. Consent of parents (or the person with parental authority in families): signed and dated written informed consent.

Exclusion Criteria:

  1. Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
  2. Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
  3. Patients had a history of a major surgery within 2 weeks before enrollment;
  4. Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
  5. Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
  6. Concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
  7. Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.

  8. Patients with inadequate liver function:

    Total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age.

  9. Patients with inadequate renal function:

    0-5 years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-14 years of age maximum serum creatinine (mg/dL) of 1.2;

  10. Adequate bone marrow function:

    Absolute neutrophil count lower than 1 × 109/L;

  11. History of a malignancy within 5 years;
  12. HIV infection or known immunodeficiency;
  13. Indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than IH;
  14. Patients with an inability to participate in or follow-up during the study treatment and assessment plan;
  15. Inability to give informed consent.

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low dose of sirolimus
Sirolimus The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 1 year.
Drug: Sirolimus
Use of different doses of the same drug
Other Names:
  • Rapamycin
  • Rapamune
Active Comparator: High dose of sirolimus
Sirolimus The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year.
Drug: Sirolimus
Use of different doses of the same drug
Other Names:
  • Rapamycin
  • Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients achieving an objective response at month 12
Time Frame: 12 months
Objective response was defined as ≥20% reduction in KHE volume compared to that at baseline.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
lesion responses
Time Frame: 12 months

The primary endpoint was classified as follow:

  • Complete involution: 100% resolution of the measured KHE;
  • Nearly complete involution was defined as decrease of ≥75% and <100%;
  • Partial involution was defined as decrease of ≥20% and <75%;
  • No change was defined as <20% increase and <20% decrease in the volumes of KHE lesions;
  • Further growth was defined as ≥20% increase in the volume of index KHE compared with the baseline volume measured. Lesion responses were overall lesion response rate and good lesion response rate.

Overall lesion response comprised complete, nearly complete and partial involutions.

Good lesion response comprised complete and nearly complete involutions.
12 months
Quality of life (QOL) in patients
Time Frame: 12 months
Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Infant Scales (<2 years) or Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Scales (2-18 years) were used.
12 months
Disease sequelae
Time Frame: 12 months
Disease sequelae (e.g., chronic pain, lymphedema and decreased ROM) were assessed by site investigators at month 12. The site investigators assessed patients' extremity swelling (if any), general physical activity and exercise levels. The diagnosis of lymphedema was based on physical examination (e.g., Stemmer's sign) and lymphoscintigraphic findings.
12 months
Frequency of adverse events
Time Frame: 12 months
Frequency of adverse events (e.g. gastrointestinal disorders, blood and lymphatic system disorders, metabolic disorders or other abnormal laboratory results, skin disorders and general disorders, etc.) collected by investigator and reported by parents. All adverse events were collected and graded according to Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). The causality of the adverse event was determined by the multidisciplinary staff and was classified as definitively not related, probably not related, possibly related, probably related, or definitively related. Any dose reductions, interruptions, or cessations enacted at the discretion of the investigators were recorded.
12 months
The changes of fibrinogen and D-dimer levels
Time Frame: 12 months
Fibrinogen and D-dimer levels
12 months

Collaborators and Investigators

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

Sponsor

West China Hospital

Investigators

  • Principal Investigator: Yi Ji, MD, PhD, West China Hospital

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 (Actual)

February 17, 2021

Primary Completion (Actual)

August 10, 2023

Study Completion (Actual)

August 10, 2023

Study Registration Dates

First Submitted

February 19, 2021

First Submitted That Met QC Criteria

February 25, 2021

First Posted (Actual)

March 1, 2021

Study Record Updates

Last Update Posted (Actual)

May 7, 2024

Last Update Submitted That Met QC Criteria

May 5, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-217

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

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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