- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04598204
Efficacy and Safety of Rapamycin to Complex Vascular Anomalies in Pediatric Patients
A Phase II Clinical Study to Evaluate the Efficacy and Safety of Rapamycin in Complex Vascular Anomalies in Pediatric Patients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Yang Lihua
- Phone Number: 13580532469
- Email: dryanglihua@163.com
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510280
- Recruiting
- Zhujiang Hospital
-
Contact:
- Wu xiaoxiao
- Phone Number: +86-13826084545
- Email: zjllwyh@sina.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis: All patients must be diagnosed with Kaposiform Hemangioendotheliomas ,Tufted Angioma or complicated vascular malformation as determined by clinical, radiographic and histologic criteria (when possible);
- Patients must have vascular anomalies that respond poorly to propranolol hydrochloride and corticosteroid;
Organ function requirements:
3.1 Adequate liver function defined as: Total bilirubin (sum of conjugated and unconjugated) ≤1.5 x ULN for age, and SGPT (ALT) <5 x ULN for age, and Serum albumin > or = 2 g/dL.
3.2 Adequate Bone Marrow Function defined as: Peripheral absolute neutrophil count (ANC) > or = 1000/microL Hemoglobin > or = 8.0 gm/dL (may receive RBC transfusions) Platelet count > or = 50,000/microL (transfusion independent defined as not receiving a platelet transfusion within a 7 day period prior to enrollment) (Note: There is NO platelet requirement for patients with Kasabach-Merritt Phenomenon) 3.3 Adequate Renal Function Defined as:
A serum creatinine based on age as follows:
≤ 5 years of age maximum serum creatinine (mg/dL) of 0.8 6 < age ≤ 10 years of age maximum serum creatinine (mg/dL) of 1.0 11 < age ≤ 15 years of age maximum serum creatinine (mg/dL) of 1.2 > 15 years of age maximum serum creatinine (mg/dL) of 1.5 cystatin C equal to or less than the upper limit of normal for the patient. If cystatin C does not initially meet this criterion, it may be repeated or a more sensitive screening by nuclear GFR must be ≥ 70 ml/min.
Urine protein to creatinine ratio (UPC) < 0.3 g/l
- Patients must be Human Immunodeficiency Virus negative and without immunodeficiency or infectious disease such as viral hepatitis.
- Patients must have no gastrointestinal disease that would affect the absorption of rapamycin.
- Performance Status: Karnofsky > or = 50 (>10 years of age) and Lansky > or = 50 for patients < or = 10 years of age.
- Patients may not be currently receiving strong inhibitors of CYP3A4 or strong inducers of CYP3A4 and may not have received these medications within 1 week of entry.
- Patients must not have corticosteroid, chemotherapy or radiotherapy within 2 weeks of entry.
- Guardians must be informed consent.
Exclusion Criteria:
- Known allergy to mTOR inhibitor
- Under the treatment of other medicine for vascular anomalies.
- Known chronic or infectious disease.
- Patients who received prior per os treatment with an mTOR inhibitor.
- Known digestive disease that would affect the absorption of rapamycin.
- Guardians disagree to sign the informed consent.
- Patients who in the opinion of the investigator would be at risk in the study or would affect the accuracy of the study results.-
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment Arm
To treat the enrolled patients with oral rapamycin at an initial dosage of 0.8mg/m2, once daily for children under 3 years old and twice daily (every 12 hours) for those above 3 years, and adjust the dosage to target a trough concentration of rapamycin in plasma as 10-15ng/ml (OR 15-20ng/ml if the efficacy of treatment is not satisfactory).
One course lasts for 12weeks and no more than 4 course is given.
|
To treat the enrolled patients with oral rapamycin with an initial dosage of 0.8mg/m2, once daily for children under 3 years old and twice daily (every 12 hours) for those above 3 years, and adjust the dosage to target a trough concentration of rapamycin in plasma as 10-15ng/ml (OR 15-20ng/ml if the efficacy of treatment is not satisfactory).
One course lasts for 12weeks and no more than 4 course is given.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Volumetric changes in complicated vascular anomalies after rapamycin treatment
Time Frame: Baseline,and every 6 months until half a year after the finish of rapamycin treatment
|
Response to rapamycin treatment was measured by volumetric magnetic resonance imaging (MRI) and/or ultrasonography analyses.
Changes in size of vascular anomalies were classified as further growth (increase of ≥20%), no change (<20% increase and <20% decrease),and involution (decrease of ≥20%).
|
Baseline,and every 6 months until half a year after the finish of rapamycin treatment
|
Time of clinical lab indexes to be improved and stable
Time Frame: at least weekly before a improved and stable state is reached,assessed up to 8 weeks
|
For cases complicated with Kasabach-Merritt Phenomenon, clinical lab indexes including blood platelet and fibrinogen are followed up at least weekly before a improved and stable state is reached.
Time (days) from the onset of treatment till these indexes to be improved and stable is calculated.
Improved hematologic parameters are defined as a platelet count greater than 50,000/uL (or a 2 times increase in platelet count compared to baseline) and a fibrinogen level greater than 100mg/dl.
|
at least weekly before a improved and stable state is reached,assessed up to 8 weeks
|
Occurrence of adverse reactions
Time Frame: From the date of trial until the date of first documented progression or date of lost to follow-up,till half a year after finish of treatment.
|
Record the time, degree and outcome of adverse reactions according to Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
|
From the date of trial until the date of first documented progression or date of lost to follow-up,till half a year after finish of treatment.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Trough concentration of rapamycin in plasma
Time Frame: 5 days after the onset of rapamycin or after the adjustment of drug doses;every 3 three months during the therapy if the concentration result is in the optimal target range during the treatment,assessed up to 100 months.
|
Trough concentration of rapamycin in plasma is monitored and according to which the dosage is adjusted,thus is part of the efficacy evaluation.
|
5 days after the onset of rapamycin or after the adjustment of drug doses;every 3 three months during the therapy if the concentration result is in the optimal target range during the treatment,assessed up to 100 months.
|
Evolution of clinical situation and the quality of life
Time Frame: Baselin,3,6,12months,and till half an year after finish of treatment
|
Evolution of clinical situation and the quality of life is judged by the proxies of patients by describing clinical symptoms and by recording and viewing standardized digital photographs.
|
Baselin,3,6,12months,and till half an year after finish of treatment
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-EKZX-003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Vascular Anomalies
-
Nemours Children's ClinicRecruitingVascular AnomalyUnited States
-
West China HospitalCompleted
-
University of California, San FranciscoCompletedSkeletal Anomalies | Multiple Anomalies | Structural Anomalies | Cardiac Anomalies | Central Nervous System Anomalies | Thorax Anomalies | Genito-urinary Anomalies | Gastrointestinal AnomaliesUnited States
-
Medical College of WisconsinChildren's Hospital and Health System Foundation, WisconsinTerminated
-
Children's Hospital of Fudan UniversityRecruitingKaposiform Hemangioendothelioma | Tufted Angioma | Superficial Vascular Anomalies | Superficial Lymphatic MalformationsChina
-
Aljazeera HospitalKasr El Aini Hospital; National Research Centre, EgyptUnknown
-
Assiut UniversityRecruitingMullerian Duct AnomaliesEgypt
-
University of California, San FranciscoEnrolling by invitationFetal Structural AnomaliesUnited States
-
Ziekenhuis Oost-LimburgCompletedAnomalies VascularBelgium
-
Centre Hospitalier Universitaire DijonCompletedCoronary Artery Bypass Graft | Anomalies in Glucose MetabolismFrance
Clinical Trials on Treatment with oral rapmycin
-
Odense University HospitalNovo Nordisk A/S; Department of Nephrology, Odense University Hospital; The A... and other collaboratorsRecruitingKidney Failure, Chronic | Kidney Injury | Risk Reduction | Contrast-induced NephropathyDenmark
-
Institut Cancerologie de l'OuestFondation ARC; University of Angers, GRANEMUnknownStage III Renal Cell Cancer | Metastatic Renal CancerFrance
-
Rigshospitalet, DenmarkCompleted
-
Université de MontréalSt. Justine's HospitalTerminatedObstructive Sleep ApneaCanada
-
National Cheng-Kung University HospitalRecruitingPneumonia, Bacterial | Oral HygieneTaiwan
-
Universidad Complutense de MadridRecruitingMalocclusion, Angle Class II | DistalizationSpain
-
Hospital Universitari Vall d'Hebron Research InstituteCompletedLiposomated Iron | Y-de-Roux Gastric By-Pass | Parenteral Iron TherapySpain
-
Xuanwu Hospital, BeijingCompletedSleep Apnea Syndromes | Atherosclerosis | Carotid Plaque
-
University of California, San FranciscoCompletedChlamydia | TrachomaEthiopia
-
Raincy Montfermeil Hospital GroupNot yet recruiting