Different Doses of Sirolimus for the Maintenance Treatment of Kaposiform Hemangioendothelioma

NCT ID: NCT05324384

Last Updated: 2024-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-05

Study Completion Date

2025-11-30

Brief Summary

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The purpose of this study is to compare the efficacy and safety of different doses of sirolimus in the maintenance treatment of kaposiform hemangioendothelioma.

Detailed Description

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Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular neoplasm that occurs predominantly in infancy or early childhood, with an incidence of approximately 0.071/100,000. 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, while 10-15 ng/ml is the most commonly used blood concentration. However, long-term higher dose sirolimus treatment can cause some common adverse effects, 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. Previous studies have found good efficacy of low-dose sirolimus maintenance treatment for KHE. However, there is no high-level evidence to support this treatment strategy. Therefore, we conducted this study to find out whether an early reduction in sirolimus dose would benefit the prognosis of the patients.

Conditions

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Hemangioendothelioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Low dose of sirolimus

The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 6 months. Then, The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 6 months.

Group Type EXPERIMENTAL

Sirolimus

Intervention Type DRUG

Use of different doses of the same drug

Regular 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.

Group Type ACTIVE_COMPARATOR

Sirolimus

Intervention Type DRUG

Use of different doses of the same drug

Interventions

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Sirolimus

Use of different doses of the same drug

Intervention Type DRUG

Other Intervention Names

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Rapamycin Rapamune

Eligibility Criteria

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Inclusion Criteria

Presenting a KHE with the following characteristics:

1. Male and female;
2. Between 0 and 14 years of age;
3. Diagnosis of KHE as determined by:

* Biopsy;
* Compatible MRI findings;
* History and clinical features.
4. Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
5. 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.
Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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West China Hospital

OTHER

Sponsor Role lead

Responsible Party

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Yi Ji

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yi Ji, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

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West China Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yi Ji, MD, PhD

Role: CONTACT

86 28 85423453

Siyuan Chen, MD, PhD

Role: CONTACT

86 28 85422215

Facility Contacts

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Yi Ji, MD, PhD

Role: primary

+86 28 85423453

Siyuan Chen, MD, PhD

Role: backup

+862885422215

References

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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.

Reference Type RESULT
PMID: 32014025 (View on PubMed)

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.

Reference Type RESULT
PMID: 31489702 (View on PubMed)

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.

Reference Type RESULT
PMID: 28486787 (View on PubMed)

Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB, Trenor CC 3rd. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. J Pediatr. 2013 Jan;162(1):142-7. doi: 10.1016/j.jpeds.2012.06.044. Epub 2012 Aug 4.

Reference Type RESULT
PMID: 22871490 (View on PubMed)

Rossler J, Baselga E, Davila V, Celis V, Diociaiuti A, El Hachem M, Mestre S, Haeberli D, Prokop A, Hanke C, Loichinger W, Quere I, Baumgartner I, Niemeyer CM, Kapp FG. Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13.

Reference Type RESULT
PMID: 33580918 (View on PubMed)

Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood. 2022 Mar 17;139(11):1619-1630. doi: 10.1182/blood.2021014027.

Reference Type RESULT
PMID: 35030255 (View on PubMed)

Other Identifiers

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2022-405

Identifier Type: -

Identifier Source: org_study_id

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