Efficacy of Rapamycin (Sirolimus) in the Treatment of BRBNS, Hereditary or Sporadic Venous Malformation

Peking Union Medical College Hospital20 enrolled

Overview

A prospective, nonrandomized, open-label, single-arm clinical trial to study efficacy of rapamycin (sirolimus) in the treatment of Blue Rubber Bleb Nevus Syndrome, hereditary or sporadic venous malformation

Blue rubber bleb nevus syndrome (BRBNS) and venous malformation are mainly caused by somatic mutation of TEK and PIK3CA, which activates the PI3K/AKT signaling pathway. As an important protein kinase downstream of the PI3K/AKT pathway, mTOR can serve as a potential therapeutic target for BRBNS. Experiments of mice have shown that rapamycin inhibited the progression of venous malformation lesions. There are a few human cases reported using rapamycin treatment. The investigator's study is designed to be a prospective, nonrandomized, open-label, single-arm clinical trial to investigate its efficacy and safety.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Blue Rubber Bleb Nevus Syndrome Venous Malformation

Interventions

RapamycinDRUG

For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * Patients diagnosed with BRBNS, VMCM, sporadic multiple VM, or large single VM; * Age and gender are not limited; * Physical status ECOG 0\~3; * Organ function is good, biochemical examination meets the following conditions: AST ≤ 2.5 × upper limit of normal value (ULN), ALT ≤ 2.5 × upper limit of normal value (ULN), serum total bilirubin ≤ 1.5 × upper limit of normal value (ULN), creatinine ≤ 1.5 × upper limit of normal (ULN); * Patients volunteer to participate in the trial and sign the informed consent form by the participant or his/her legal guardian. Exclusion Criteria: * Patients need emergency surgery due to intestinal obstruction, intussusception, or gastrointestinal bleeding; * History of surgery within 1 month; * allergic to rapamycin; * Any disease or condition that may affect the study implementation or result interpretation, including: known hemoglobinopathy, suffering from gastrointestinal infections at the same time, severe heart, liver, kidney and other serious concomitant diseases that may endanger lives * Pregnant or lactating women; * Alcohol or drugs (eg, laxatives) abusers; * Participating in another clinical trial that may affect this study within one month; * Being believed not suitable to be enrolled by the investigator for other reasons. Exit Criteria: * An allergic reaction to rapamycin occurs. * The patient requests withdrawal: at his own discretion or at the request of his legal representative. Subjects may refuse to participate in further studies at any time without reasons. Subjects will not be affected because of such decision. * Subjects are required to withdraw from the study in certain special circumstances (eg, there is significant issues of compliance, safety, or surgical intervention for the disease) * Other situations in which the study must be terminated. For example, the investigators believe that continuing the study may be harmful to the health of subjects. Rejection Criteria: * Patients who violate the requirements of the test protocol * Patients with poor recording (with incomplete, or inaccurate data)

Locations (1)

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

Beijing, Beijing Municipality, China

RECRUITING

Outcomes

Primary Outcomes

Total venous malformation lesion load

lesion load (cm2) = A + B + C. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by chest, abdomen and pelvis MRI or small bowel CT reconstruction (in cm2) B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2) C = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by ultrasound (in cm2) Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment.