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

NCT ID: NCT04775173

Last Updated: 2024-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-17
• Study Completion Date: 2023-08-10

Brief 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.

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.

Conditions

Kaposiform Hemangioendothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Sirolimus

Intervention Type: DRUG

Use of different doses of the same drug

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.

Group Type: ACTIVE_COMPARATOR

Sirolimus

Intervention Type: DRUG

Use of different doses of the same drug

Interventions

Sirolimus

Use of different doses of the same drug

Intervention Type: DRUG

Other Intervention Names

Rapamycin; Rapamune

Eligibility Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yi Ji

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yi Ji, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Countries

China

References

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)

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)

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.

Reference Type: RESULT

PMID: 29388191 (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)

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.

Reference Type: RESULT

PMID: 30396415 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31030813 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23796341 (View on PubMed)

Other Identifiers

2021-217

Identifier Type: -

Identifier Source: org_study_id