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

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhujiang Hospital

Criteria

Inclusion Criteria:

1. 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)；

2. Patients must have vascular anomalies that respond poorly to propranolol hydrochloride and corticosteroid;

3. 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

4. Patients must be Human Immunodeficiency Virus negative and without immunodeficiency or infectious disease such as viral hepatitis.

5. Patients must have no gastrointestinal disease that would affect the absorption of rapamycin.

6. Performance Status: Karnofsky > or = 50 (>10 years of age) and Lansky > or = 50 for patients < or = 10 years of age.

7. 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.

8. Patients must not have corticosteroid, chemotherapy or radiotherapy within 2 weeks of entry.

9. Guardians must be informed consent.

Exclusion Criteria:

1. Known allergy to mTOR inhibitor

2. Under the treatment of other medicine for vascular anomalies.

3. Known chronic or infectious disease.

4. Patients who received prior per os treatment with an mTOR inhibitor.

5. Known digestive disease that would affect the absorption of rapamycin.

6. Guardians disagree to sign the informed consent.

7. Patients who in the opinion of the investigator would be at risk in the study or would affect the accuracy of the study results.-