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

NCT ID: NCT03767660

Last Updated: 2018-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-31

Study Completion Date

2022-07-01

Brief Summary

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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

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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.

Conditions

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Blue Rubber Bleb Nevus Syndrome Venous Malformation

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Rapamycin

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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Sirolimus

Eligibility Criteria

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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)
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Air Force General Hospital of the PLA

OTHER_GOV

Sponsor Role collaborator

Chinese Academy of Medical Sciences

OTHER

Sponsor Role collaborator

Peking Union Medical College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jiaolin Zhou, MD

Role: CONTACT

Phone: 13910136704

Email: [email protected]

Facility Contacts

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Jiaolin Zhou, MD

Role: primary

References

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Soblet J, Kangas J, Natynki M, Mendola A, Helaers R, Uebelhoer M, Kaakinen M, Cordisco M, Dompmartin A, Enjolras O, Holden S, Irvine AD, Kangesu L, Leaute-Labreze C, Lanoel A, Lokmic Z, Maas S, McAleer MA, Penington A, Rieu P, Syed S, van der Vleuten C, Watson R, Fishman SJ, Mulliken JB, Eklund L, Limaye N, Boon LM, Vikkula M. Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9.

Reference Type BACKGROUND
PMID: 27519652 (View on PubMed)

Ochiai D, Miyakoshi K, Yakubo K, Fukuiya T, Yoshimura Y. Familial blue rubber bleb nevus syndrome in pregnancy with spinal epidural involvement. Case Rep Obstet Gynecol. 2013;2013:141506. doi: 10.1155/2013/141506. Epub 2013 May 9.

Reference Type BACKGROUND
PMID: 23762681 (View on PubMed)

Carvalho S, Barbosa V, Santos N, Machado E. Blue rubber-bleb nevus syndrome: report of a familial case with a dural arteriovenous fistula. AJNR Am J Neuroradiol. 2003 Oct;24(9):1916-8.

Reference Type BACKGROUND
PMID: 14561629 (View on PubMed)

Kisu T, Yamaoka K, Uchida Y, Mori H, Nakama T, Hisatsugu T, Miyaji H, Motooka M. A case of blue rubber bleb nevus syndrome with familial onset. Gastroenterol Jpn. 1986 Jun;21(3):262-6. doi: 10.1007/BF02774569.

Reference Type BACKGROUND
PMID: 3732758 (View on PubMed)

Jin XL, Wang ZH, Xiao XB, Huang LS, Zhao XY. Blue rubber bleb nevus syndrome: a case report and literature review. World J Gastroenterol. 2014 Dec 7;20(45):17254-9. doi: 10.3748/wjg.v20.i45.17254.

Reference Type BACKGROUND
PMID: 25493043 (View on PubMed)

Dobru D, Seuchea N, Dorin M, Careianu V. Blue rubber bleb nevus syndrome: case report and literature review. Rom J Gastroenterol. 2004 Sep;13(3):237-40.

Reference Type BACKGROUND
PMID: 15470538 (View on PubMed)

Boscolo E, Limaye N, Huang L, Kang KT, Soblet J, Uebelhoer M, Mendola A, Natynki M, Seront E, Dupont S, Hammer J, Legrand C, Brugnara C, Eklund L, Vikkula M, Bischoff J, Boon LM. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest. 2015 Sep;125(9):3491-504. doi: 10.1172/JCI76004. Epub 2015 Aug 10.

Reference Type BACKGROUND
PMID: 26258417 (View on PubMed)

Cardoso H, Dias JA, Silva M, Vilas-Boas F, Trindade E, Tavares M, Macedo G. 'Education and Imaging. Gastrointestinal: Successful treatment with sirolimus of a patient with blue rubber bleb nevus syndrome. J Gastroenterol Hepatol. 2016 Mar;31(3):519. doi: 10.1111/jgh.13178. No abstract available.

Reference Type BACKGROUND
PMID: 26456887 (View on PubMed)

Yuksekkaya H, Ozbek O, Keser M, Toy H. Blue rubber bleb nevus syndrome: successful treatment with sirolimus. Pediatrics. 2012 Apr;129(4):e1080-4. doi: 10.1542/peds.2010-3611. Epub 2012 Mar 5.

Reference Type BACKGROUND
PMID: 22392180 (View on PubMed)

Unlusoy Aksu A, Sari S, Egritas Gurkan O, Dalgic B. Favorable Response to Sirolimus in a Child With Blue Rubber Bleb Nevus Syndrome in the Gastrointestinal Tract. J Pediatr Hematol Oncol. 2017 Mar;39(2):147-149. doi: 10.1097/MPH.0000000000000681.

Reference Type BACKGROUND
PMID: 27820137 (View on PubMed)

Salloum R, Fox CE, Alvarez-Allende CR, Hammill AM, Dasgupta R, Dickie BH, Mobberley-Schuman P, Wentzel MS, Chute C, Kaul A, Patel M, Merrow AC, Gupta A, Whitworth JR, Adams DM. Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment. Pediatr Blood Cancer. 2016 Nov;63(11):1911-4. doi: 10.1002/pbc.26049. Epub 2016 Jun 8.

Reference Type BACKGROUND
PMID: 27273326 (View on PubMed)

Moavero R, Coniglio A, Garaci F, Curatolo P. Is mTOR inhibition a systemic treatment for tuberous sclerosis? Ital J Pediatr. 2013 Sep 17;39:57. doi: 10.1186/1824-7288-39-57.

Reference Type BACKGROUND
PMID: 24044547 (View on PubMed)

McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.

Reference Type BACKGROUND
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Paul E, Thiele E. Efficacy of sirolimus in treating tuberous sclerosis and lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):190-2. doi: 10.1056/NEJMe0707153. No abstract available.

Reference Type BACKGROUND
PMID: 18184966 (View on PubMed)

Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM, Schmithorst VJ, Laor T, Brody AS, Bean J, Salisbury S, Franz DN. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):140-51. doi: 10.1056/NEJMoa063564.

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Reference Type BACKGROUND
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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HS-1606

Identifier Type: -

Identifier Source: org_study_id