Efficacy and Safety of Different Concentrations of Sirolimus in the Treatment of Kaposiform Hemangioendothelioma.
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| ClinicalTrials.gov Identifier: NCT04775173 |
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Recruitment Status :
Recruiting
First Posted : March 1, 2021
Last Update Posted : January 18, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Kaposiform Hemangioendothelioma | Drug: Sirolimus | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 30 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Efficacy and Safety of Different Concentrations of Sirolimus in the Treatment of Kaposiform Hemangioendothelioma. |
| Actual Study Start Date : | February 17, 2021 |
| Estimated Primary Completion Date : | August 20, 2023 |
| Estimated Study Completion Date : | August 20, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Low dose of sirolimus
Sirolimus The plasma trough concentration of sirolimus is maintained within the range of 5-10 ng/ml by adjusting sirolimus dose, for 1 year.
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Drug: Sirolimus
Use of different doses of the same drug
Other Names:
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Active Comparator: 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.
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Drug: Sirolimus
Use of different doses of the same drug
Other Names:
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- The changes in KHE volume [ Time Frame: Baseline, 3, 6, and 12 months ]
Response to therapy was measured by volumetric magnetic resonance imaging (MRI) analyses were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in KHE size were classified as further growth (increase of ≥10%), no change (<10% increase and <10% decrease), partial involution (decrease of ≥10% and <75%), nearly complete involution (decrease of ≥75% and <100%), or complete involution (100%).
Photographs of the mixed KHE were taken at months 0, 6 and 12 by a medical photographer.
- The changes of platelet counts [ Time Frame: Baseline, 1, 3, 6, and 12 months ]Platelet counts
- The changes of fibrinogen levels [ Time Frame: Baseline, 1, 3, 6, and 12 months ]Fibrinogen levels
- Quality of life (QOL) in patients [ Time Frame: 6 and 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.
- The changes in the patient's musculoskeletal complication. [ Time Frame: Baseline, 3, 6, and 12 months ]The severity of musculoskeletal complication was scored by using a 4-point scale: 1, asymptomatic or mild symptoms, clinical or diagnostic observations only; 2, moderate symptoms, limiting age-appropriate instrumental activities of daily living; 3, severe or medically significant symptoms, disabling or limiting self-care activities of daily living; and 4, life-threatening consequences, with urgent intervention indicated.
- 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 4.0 (CTCAE v4.0). 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.
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| Ages Eligible for Study: | 1 Day to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Presenting a KHE with the following characteristics:
- Clinical features and histological findings consistent with progressive, non-resectable KHE.
- Patients must be 0 - 18 years of age at the time of study entry.
- Adequate liver function: a. Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age, and; b. ALT and AST less than or equal to 2.5 x upper limit normal (ULN) for age.
- Adequate renal function: a. 0-5 years of age maximum serum creatinine (mg/dL) of 0.8; b. 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; c. 11-15 years of age maximum serum creatinine (mg/dL) of 1.2; d. 16-18 years of age maximum serum creatinine (mg/dL) of 1.5.
- Adequate bone marrow function: Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 to the ninth/Liter.
- Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.
Exclusion Criteria:
- Allergy to sirolimus or other rapamycin analogues.
- Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization.
- Patients must not be known to be Human Immunodeficiency Virus positive or known immunodeficiency. Testing is not required unless a condition is suspected.
- Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
- Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
- Patients who have a history of malignancy.
- Patients with an inability to participate or to follow the study treatment and assessment plan.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04775173
| Contact: Yi Ji, MD, PhD | 86 28 85423453 | jijiyuanyuan@163.com | |
| Contact: Siyuan Chen, MD, PhD | 86 28 85422215 | siy_chen@163.com |
| China, Sichuan | |
| West China Hospital of Sichuan University | Recruiting |
| Chengdu, Sichuan, China, 610041 | |
| Contact: Yi Ji, MD, PhD +86 28 85423453 jijiyuanyuan@163.com | |
| Contact: Siyuan Chen, MD, PhD +862885422215 siy_chen@163.com | |
| Principal Investigator: Yi Ji, MD, PhD | |
| Sub-Investigator: Jiangyuan Zhou, MD | |
| Sub-Investigator: Kaiying Yang, MD | |
| Sub-Investigator: Tong Qiu, MD | |
| Sub-Investigator: Xue Gong, MD | |
| Principal Investigator: | Yi Ji, MD, PhD | West China Hospital |
| Responsible Party: | Yi Ji, Clinical Professor, West China Hospital |
| ClinicalTrials.gov Identifier: | NCT04775173 |
| Other Study ID Numbers: |
2021-217 |
| First Posted: | March 1, 2021 Key Record Dates |
| Last Update Posted: | January 18, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Kaposiform Hemangioendothelioma Sirolimus Efficacy Safety |
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Hemangioendothelioma Sarcoma, Kaposi Kasabach-Merritt Syndrome Hemangioma Neoplasms, Vascular Tissue Neoplasms by Histologic Type Neoplasms Herpesviridae Infections DNA Virus Infections Virus Diseases Infections Sarcoma Neoplasms, Connective and Soft Tissue |
Thrombocytopenia Blood Platelet Disorders Hematologic Diseases Sirolimus Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antineoplastic Agents Antifungal Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |