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

December 17, 2018 updated by: Peking Union Medical College Hospital

Efficacy of Rapamycin (Sirolimus) in the Treatment of Blue Rubber Bleb Nevus Syndrome, Hereditary or Sporadic Venous Malformation

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Anticipated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100000
        • Recruiting
        • Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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: Rapamycin
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
Drug: Rapamycin
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
Other Names:
  • Sirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total venous malformation lesion load
Time Frame: The time from start of therapy to 1 year
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.
The time from start of therapy to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amount of daily oral iron supplements
Time Frame: The time from start of therapy to 1 year
The value indicates the amount of gastrointestinal bleeding.
The time from start of therapy to 1 year
Concentration of hemoglobin in blood
Time Frame: The time from start of therapy to 1 year
The value indicates the amount of gastrointestinal bleeding.
The time from start of therapy to 1 year
Frequency of blood transfusion
Time Frame: The time from start of therapy to 1 year
The value indicates the amount of gastrointestinal bleeding
The time from start of therapy to 1 year
Concentration of D-dimer in blood
Time Frame: The time from start of therapy to 1 year
The value indicates the extent of local coagulation caused by Venous Malformation lesions.
The time from start of therapy to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Air Force General Hospital of the PLA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2018

Primary Completion (Anticipated)

January 1, 2022

Study Completion (Anticipated)

July 1, 2022

Study Registration Dates

First Submitted

November 24, 2018

First Submitted That Met QC Criteria

December 5, 2018

First Posted (Actual)

December 6, 2018

Study Record Updates

Last Update Posted (Actual)

December 19, 2018

Last Update Submitted That Met QC Criteria

December 17, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-1606

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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