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Kaposiform HemangioendotheliomaPhase 2NCT04775173

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

A Phase 2 study testing Sirolimus in people with Kaposiform Hemangioendothelioma, run by West China Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 1 day to 14 years
Conditions the study is for
Kaposiform Hemangioendothelioma
What is being tested?
Sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
79 participants
Where
1 siteChina
Study dates
17 Feb 2021to 10 Aug 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 day to 14 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Presenting a KHE with the following characteristics:
  • Male and female;
  • Between 0 and 14 years of age;
  • 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;
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  • 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.
  • Without KMP, which was defined as a platelet count of less than 100×10^9/L, with consumptive coagulopathy and hypofibrinogenemia.
  • Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
  • Consent of parents (or the person with parental authority in families): signed and dated written informed consent.

Who cannot join

  • Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
  • Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
  • Patients had a history of a major surgery within 2 weeks before enrollment;
  • Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
  • Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
  • 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).
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  • Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
  • 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.
  • 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;
  • Adequate bone marrow function:
  • Absolute neutrophil count lower than 1 × 109/L;
  • History of a malignancy within 5 years;
  • HIV infection or known immunodeficiency;
  • Indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than IH;
  • Patients with an inability to participate in or follow-up during the study treatment and assessment plan;
  • Inability to give informed consent.

Trial locations and contacts

1 site in 1 country.

China1 site

  • West China Hospital of Sichuan University

    Chengdu, Sichuan, 610041

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
Sirolimus
Keywords
Kaposiform Hemangioendothelioma, Sirolimus, Efficacy, Safety
Medical subject headings
Kaposiform Hemangioendothelioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SirolimusDrug

    Also called Rapamycin, Rapamune

    Use of different doses of the same drug

Study groups in NCT04775173
Study groupRoleWhat they receive
Low dose of sirolimusExperimentalSirolimus The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 1 year.
Receives: Drug: Sirolimus
High dose of sirolimusActive comparatorSirolimus The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year.
Receives: Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of patients achieving an objective response at month 12

    Objective response was defined as ≥20% reduction in KHE volume compared to that at baseline.

    Measured: 12 months

Secondary outcomes (5)

  1. lesion responses

    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.

    Measured: 12 months

  2. Quality of life (QOL) in patients

    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.

    Measured: 12 months

  3. Disease sequelae

    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.

    Measured: 12 months

  4. Frequency of adverse events

    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.

    Measured: 12 months

  5. The changes of fibrinogen and D-dimer levels

    Fibrinogen and D-dimer levels

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2021
  2. Study start17 Feb 2021
  3. Primary completion10 Aug 2023
  4. Study completion10 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
79 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04775173
Sponsor's protocol ID
2021-217
Status last verified
May 2024
First submitted
19 Feb 2021
Last updated
7 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ji Y, Chen S, Yang K, Xia C, Li L. Kaposiform hemangioendothelioma: current knowledge and future perspectives. Orphanet J Rare Dis. 2020 Feb 3;15(1):39. doi: 10.1186/s13023-020-1320-1.

    PubMed 32014025

  • Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.

    PubMed 28486787

  • Zhang G, Chen H, Gao Y, Liu Y, Wang J, Liu XY. Sirolimus for treatment of Kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon: a retrospective cohort study. Br J Dermatol. 2018 May;178(5):1213-1214. doi: 10.1111/bjd.16400. Epub 2018 Mar 25. No abstract available.

    PubMed 29388191

  • Wang Z, Yao W, Sun H, Dong K, Ma Y, Chen L, Zheng S, Li K. Sirolimus therapy for kaposiform hemangioendothelioma with long-term follow-up. J Dermatol. 2019 Nov;46(11):956-961. doi: 10.1111/1346-8138.15076. Epub 2019 Sep 5.

    PubMed 31489702

  • Johnson AB, Richter GT. Vascular Anomalies. Clin Perinatol. 2018 Dec;45(4):737-749. doi: 10.1016/j.clp.2018.07.010. Epub 2018 Sep 18.

    PubMed 30396415

  • Adams DM, Ricci KW. Vascular Anomalies: Diagnosis of Complicated Anomalies and New Medical Treatment Options. Hematol Oncol Clin North Am. 2019 Jun;33(3):455-470. doi: 10.1016/j.hoc.2019.01.011.

    PubMed 31030813

  • Drolet BA, Trenor CC 3rd, Brandao LR, Chiu YE, Chun RH, Dasgupta R, Garzon MC, Hammill AM, Johnson CM, Tlougan B, Blei F, David M, Elluru R, Frieden IJ, Friedlander SF, Iacobas I, Jensen JN, King DM, Lee MT, Nelson S, Patel M, Pope E, Powell J, Seefeldt M, Siegel DH, Kelly M, Adams DM. Consensus-derived practice standards plan for complicated Kaposiform hemangioendothelioma. J Pediatr. 2013 Jul;163(1):285-91. doi: 10.1016/j.jpeds.2013.03.080. No abstract available.

    PubMed 23796341

  • Xu Y, Zhou J, Lan Y, Yang L, Zhang Y, Ji Y. High Responsiveness of Head and Neck Kaposiform Hemangioendothelioma Without Kasabach-Merritt Phenomenon to Sirolimus Monotherapy. Pediatr Blood Cancer. 2026 Aug 27:e70635. doi: 10.1002/1545-5017.70635. Online ahead of print.

    PubMed 42657977

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sirolimus in people with Kaposiform Hemangioendothelioma, run by West China Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients achieving an objective response at month 12 (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04775173, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.

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