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

Primary Purpose

Blue Rubber Bleb Nevus Syndrome, Venous Malformation

Status

Unknown status

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Rapamycin

About this trial

This is an interventional treatment trial for Blue Rubber Bleb Nevus Syndrome focused on measuring Blue Rubber Bleb Nevus Syndrome, Venous Malformation, Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Peking Union Medical College Hospital, Chinese Academy of Medicine SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rapamycin

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Amount of daily oral iron supplements

The value indicates the amount of gastrointestinal bleeding.

Concentration of hemoglobin in blood

The value indicates the amount of gastrointestinal bleeding.

Frequency of blood transfusion

The value indicates the amount of gastrointestinal bleeding

Concentration of D-dimer in blood

The value indicates the extent of local coagulation caused by Venous Malformation lesions.

Full Information

NCT ID

NCT03767660

First Posted

November 24, 2018

Last Updated

December 17, 2018

Sponsor

Peking Union Medical College Hospital

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03767660

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Unknown status

Study Start Date

July 31, 2018 (Actual)

Primary Completion Date

January 1, 2022 (Anticipated)

Study Completion Date

July 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Peking Union Medical College Hospital

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Blue Rubber Bleb Nevus Syndrome, Venous Malformation

Keywords

Blue Rubber Bleb Nevus Syndrome, Venous Malformation, Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Rapamycin

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rapamycin

Other Intervention Name(s)

Sirolimus

Intervention Description

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

Primary Outcome Measure Information:

Title

Total venous malformation lesion load

Description

Time Frame

The time from start of therapy to 1 year

Secondary Outcome Measure Information:

Title

Amount of daily oral iron supplements

Description

The value indicates the amount of gastrointestinal bleeding.

Time Frame

The time from start of therapy to 1 year

Title

Concentration of hemoglobin in blood

Description

The value indicates the amount of gastrointestinal bleeding.

Time Frame

The time from start of therapy to 1 year

Title

Frequency of blood transfusion

Description

The value indicates the amount of gastrointestinal bleeding

Time Frame

The time from start of therapy to 1 year

Title

Concentration of D-dimer in blood

Description

The value indicates the extent of local coagulation caused by Venous Malformation lesions.

Time Frame

The time from start of therapy to 1 year

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jiaolin Zhou, MD

Phone

13910136704

conniezhjl@yahoo.com

Facility Information:

Facility Name

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiaolin Zhou, MD

Phone

13910136704

conniezhjl@163.com

12. IPD Sharing Statement

Citations:

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27519652

Citation

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

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