Back to resultsEfficacy and Safety of Sirolimus to Vascular Anomalies
Primary Purpose
Vascular Anomaly
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Sirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Vascular Anomaly focused on measuring Sirolimus, Vascular anomalies
Eligibility Criteria
Inclusion Criteria:
All patients included in the present research must be diagnosed with one of the following vascular anomalies:
- Kaposiform Hemangioendotheliomas without Kasabach-Merritt Phenomenon
- Tufted Angioma without Kasabach-Merritt Phenomenon
- Capillary Malformations
- Lymphatic Malformations
- Venous Malformations
- Capillary-Venous Malformation (CVM)
- Capillary-Lymphatic Malformation (CLM)
- Lymphatic-Venous Malformation (LVM)
- Capillary-Lymphatic-Venous Malformation (CLVM)
- Multifocal Lymphangiomatosis and Thrombocytopenia (MLT)
- Patients must be 0 - 18 years of age at the time of study entry.
- Without functional impairment requiring treatment of corticosteroid.
- Organ function requirements:
- Adequate liver function Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x upper limit normal (ULN) for age.
- Adequate 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 11-15 years of age maximum serum creatinine (mg/dL) of 1.2 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.
- 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.
- Patients who have a history of treatment with sirolimus or other mTOR inhibitor.
Sites / Locations
- West China Hospital of Sichuan University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sirolimus
Arm Description
Outcomes
Primary Outcome Measures
Volumetric changes in complicated vascular anomalies to sirolimus
Response to sirolimus treatment was measured by volumetric magnetic resonance imaging (MRI) analyses, which were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in size of vascular anomalies 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 complicated vascular anomalies were taken at months 0, 3, 6 and 12 by a medical photographer.
Complete/nearly complete resolution of the vascular anomalies at month 12 compared to baseline based on the intra-patient blinded centralized independent qualitative assessments of month 12 MRI.
The changes in the patient's symptoms and/or complications.
Secondary Outcome Measures
Quality of Life in patients by the Pediatric Quality of Life Inventory TM (PedsQLTM) 4.0 Generic Core Scales.
The PedsQL 4.0 Generic Core Scales encompass: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items), and were developed through focus groups and cognitive interviews. The PedsQL 4.0 Generic Core Scales are comprised of parallel child self-report (ages 5-18) and parent proxy-report formats (ages 0-18). A 5-point response scale is utilized across child self-report for ages 8 to 18 and parent proxy-report (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem). For patients between ages 5-7, the response scale is simplified to a 3-point scale (0=not at all a problem; 2=sometimes a problem; 4=a lot of a problem. Items are reverse-scored and linearly transformed to a 0 to 100 scale (0=100, 1=75, 2 =50, 3=25, 4=0). Scale Scores are computed as the sum of the items divided by the number of items answered.
Measuring the impact of vascular anomalies on family functioning by PedsQLTM 4.0 Family Impact Module (FIM).
Frequency of adverse events as assessed by CTCAE v4.0
Changes in plasma levels fibrinogen and/ or D-dimers
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03583307
Brief Title
Efficacy and Safety of Sirolimus to Vascular Anomalies
Official Title
Efficacy and Safety of Sirolimus in the Treatment of the Complicated Vascular Anomalies
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
February 19, 2021 (Actual)
Study Completion Date
February 19, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
To evaluate the safety and efficacy of Sirolimus in complicated vascular anomalies in Chinese children
Detailed Description
Vascular anomalies are composed of vascular tumors and vascular malformations. The prognosis of vascular anomalies is significantly variable. Most of them had a benign course. However, complicated vascular anomalies can lead to disfigurement, organ disfunction and life-threatening with significant morbidity and mortality. Traditional treatments, including steroids, vincristine, cyclophosphamide and surgery, had limited response to complicated vascular anomalies. In the past few years, the inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway-sirolimus has emerged as a treatment for severe vascular anomalies. Besides, preclinical studies also showed that the Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR pathway play an important role in the development of vascular tumors and vascular malformations. However, the exact efficacious rate and complications of sirolimus are still unknow in china because of the lack of large scale of prospective studies. Therefore, it's important to perform this prospective study to determine the safety and efficacy of sirolimus in the treatment of Chinese children with complicated vascular anomalies, and this study will also make contributions to the diagnoses and treatments of vascular anomalies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vascular Anomaly
Keywords
Sirolimus, Vascular anomalies
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
126 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sirolimus
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Other Intervention Name(s)
Rapamycin
Intervention Description
Sirolimus was initiated at a dosage of 0.8 mg/m2 administered twice daily. Subsequently, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL.
Primary Outcome Measure Information:
Title
Volumetric changes in complicated vascular anomalies to sirolimus
Description
Response to sirolimus treatment was measured by volumetric magnetic resonance imaging (MRI) analyses, which were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in size of vascular anomalies 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 complicated vascular anomalies were taken at months 0, 3, 6 and 12 by a medical photographer.
Complete/nearly complete resolution of the vascular anomalies at month 12 compared to baseline based on the intra-patient blinded centralized independent qualitative assessments of month 12 MRI.
Time Frame
Baseline, 6, and 12 months
Title
The changes in the patient's symptoms and/or complications.
Time Frame
Baseline, 3, 6, and 12 months
Secondary Outcome Measure Information:
Title
Quality of Life in patients by the Pediatric Quality of Life Inventory TM (PedsQLTM) 4.0 Generic Core Scales.
Description
The PedsQL 4.0 Generic Core Scales encompass: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items), and were developed through focus groups and cognitive interviews. The PedsQL 4.0 Generic Core Scales are comprised of parallel child self-report (ages 5-18) and parent proxy-report formats (ages 0-18). A 5-point response scale is utilized across child self-report for ages 8 to 18 and parent proxy-report (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; 4=almost always a problem). For patients between ages 5-7, the response scale is simplified to a 3-point scale (0=not at all a problem; 2=sometimes a problem; 4=a lot of a problem. Items are reverse-scored and linearly transformed to a 0 to 100 scale (0=100, 1=75, 2 =50, 3=25, 4=0). Scale Scores are computed as the sum of the items divided by the number of items answered.
Time Frame
Baseline, 6, 12 months
Title
Measuring the impact of vascular anomalies on family functioning by PedsQLTM 4.0 Family Impact Module (FIM).
Time Frame
Baseline, 6, 12 months
Title
Frequency of adverse events as assessed by CTCAE v4.0
Time Frame
Baseline, 3, 6, 12 months
Title
Changes in plasma levels fibrinogen and/ or D-dimers
Time Frame
Baseline, 3, 6, 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients included in the present research must be diagnosed with one of the following vascular anomalies:
Kaposiform Hemangioendotheliomas without Kasabach-Merritt Phenomenon
Tufted Angioma without Kasabach-Merritt Phenomenon
Capillary Malformations
Lymphatic Malformations
Venous Malformations
Capillary-Venous Malformation (CVM)
Capillary-Lymphatic Malformation (CLM)
Lymphatic-Venous Malformation (LVM)
Capillary-Lymphatic-Venous Malformation (CLVM)
Multifocal Lymphangiomatosis and Thrombocytopenia (MLT)
Patients must be 0 - 18 years of age at the time of study entry.
Without functional impairment requiring treatment of corticosteroid.
Organ function requirements:
Adequate liver function Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x upper limit normal (ULN) for age.
Adequate 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 11-15 years of age maximum serum creatinine (mg/dL) of 1.2 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.
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.
Patients who have a history of treatment with sirolimus or other mTOR inhibitor.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yi Ji
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital of Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
61004·
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34082006
Citation
Ji Y, Chen S, Yang K, Zhou J, Zhang X, Jiang X, Xu X, Lu G, Qiu L, Kong F, Zhang Y. A prospective multicenter study of sirolimus for complicated vascular anomalies. J Vasc Surg. 2021 Nov;74(5):1673-1681.e3. doi: 10.1016/j.jvs.2021.04.071. Epub 2021 May 31.
Results Reference
derived
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Efficacy and Safety of Sirolimus to Vascular Anomalies
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