Efficacy and Safety of Rapamycin to Complex Vascular Anomalies in Pediatric Patients

NCT04598204 | Unknown Phase 2 DMC

• 1 other identifier: 2017-EKZX-003
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

KHE and TA are rare tumors and some of the cases may lead to life-threatening complications including Kasabach-Merritt Phenomenon. Typically treated with steroids and vincristine, a majority of the cases do not have good prognosis. Complex vascular malformations are always managed by surgery,sclerotherapy and embolization therapy. While many of the cases still lead to complications such as disfigurement, chronic pain, recurrent infections, coagulopathies. Different medical centers are exploring new therapy for these tough problems. This study is plotted to determine the efficacy and safety of rapamycin monotherapy in KHE/TA and complex vascular malformations in pediatric patients.

Conditions

Vascular Anomalies

Keywords

Rapamycin

Outcome Measures

Primary Outcomes (3)

• Volumetric changes in complicated vascular anomalies after 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

  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

  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 Outcomes (2)

• Trough concentration of rapamycin in plasma

  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

  Baselin,3,6,12months,and till half an year after finish of treatment

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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.

Drug: Treatment with oral rapmycin

Interventions

Treatment with oral rapmycin DRUG

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.

Treatment Arm

Eligibility Criteria

• Age: 1 Month - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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.-

Sponsors & Collaborators

• Zhujiang Hospital: lead

Study Sites (1)

Zhujiang Hospital

Guangzhou, Guangdong, 510280, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 23796341 RESULT

MeSH Terms

Conditions

Vascular Malformations

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Yang Lihua

CONTACT

13580532469; dryanglihua@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2020
• First Posted: October 22, 2020
• Study Start: December 1, 2017
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: November 10, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)