Condition or disease | Intervention/treatment | Phase |
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Vascular Malformations Lymphatic Malformation | Drug: Topical 0.1% Sirolimus Drug: Topical Vehicle | Phase 2 |
This blinded multicentre split body randomized controlled phase 2 trial aims to include 50 patients ≥ 6 years old who have a primary CMLM without an underlying malformation.
The CMLM will be divided into 2 equal areas of the same severity that will be randomly allocated to 0.1% topical sirolimus or topical vehicle for 12 weeks. During the double-blind 12-week period, both topical products will be applied by a nurse to avoid inter-group contamination and for better compliance.
At the end of the 12-week period, the patient/parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for 8 more weeks. Patients will also be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 55 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Split-body randomised, double-blind, vehicle-controlled clinical trial |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Patients, parents, nurses and investigators will be blinded for the treatment allocated to each area of the CMLM, during the first step of the study (until week 12, where primary endpoint will be assessed). To ensure the double blinding, both areas will be randomized, and the topical treatments (sirolimus and vehicle) to be applied will have similar packaging. Their appearance is similar, thus the active drug (topical sirolimus) and vehicle cannot be distinguished at drug allocation. Furthermore, the consistency of the creams is similar. |
Primary Purpose: | Treatment |
Official Title: | 0.1% Topical Sirolimus in the Treatment of Cutaneous Microcystic Lymphatic Malformations in Children and Adults: Phase II, Split-body Randomized, Double-blind, Vehicle-controlled Clinical Trial |
Actual Study Start Date : | June 5, 2019 |
Estimated Primary Completion Date : | September 2021 |
Estimated Study Completion Date : | June 2022 |
Arm | Intervention/treatment |
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Experimental: Topical sirolimus
The experimental group will consist in one area of the CMLM (almost half of it) that will receive 0.1% sirolimus preparation. This product will be applied 1/day on the randomly allocated area, by a nurse at home, during 12 weeks.
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Drug: Topical 0.1% Sirolimus
The formulation is 0.03 g rapamycin, 1.5 g Transcutol, Quantum Satis (QS) 30g Excipial® hydrocream, corresponding to a concentration at 0.1%. The cream will be packaged in 30 ml aluminium tubes.
Other Name: Verum
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Placebo Comparator: Vehicle
The control group will consist in the other half area of the CMLM, that will receive the same vehicle than the one used in the topical 0.1% sirolimus preparation. It will be applied 1/day in the corresponding area by a nurse, at home, during 12 weeks.
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Drug: Topical Vehicle
The same vehicle than the one used in the topical 0.1% sirolimus preparation will be used for the other half area of CMLM, i.e. Excipial® hydrocream. It will be packaged to maintain the double blind way of this trial and will be undistinguishable from the sirolimus cream.
Other Name: Placebo
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Ages Eligible for Study: | 6 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: MARUANI Annabel | 02 47 47 90 76 ext +33 | annabel.maruani@univ-tours.fr | |
Contact: LEDUCQ Sophie | sleducq@hotmail.fr |
France | |
ANGERS | Not yet recruiting |
Angers, France | |
Contact: MARTIN Ludovic | |
BORDEAUX | Not yet recruiting |
Bordeaux, France | |
Contact: LEAUTE-LABREZE Christine | |
LYON AD | Not yet recruiting |
Bron, France | |
Contact: GUIBAUD Laurent | |
LYON PED | Not yet recruiting |
Bron, France | |
Contact: PHAN Alice | |
CAEN | Not yet recruiting |
Caen, France | |
Contact: DOMPMARTIN Anne | |
DIJON | Not yet recruiting |
Dijon, France | |
Contact: VABRES Pierre | |
Marseille | Not yet recruiting |
Marseille, France | |
Contact: MALLET Stéphanie | |
Montpellier | Recruiting |
Montpellier, France | |
Contact: BESSIS Didier | |
NANTES | Recruiting |
Nantes, France | |
Contact: BARBAROT Sébastien | |
NICE | Not yet recruiting |
Nice, France | |
Contact: CHIAVERINI Christine | |
NECKER | Recruiting |
Paris, France | |
Contact: BOCCARA Olivia | |
QUIMPER | Not yet recruiting |
Quimper, France | |
Contact: PLANTIN Patrice | |
RENNES | Not yet recruiting |
Rennes, France | |
Contact: DROITCOURT Catherine | |
TOULOUSE | Not yet recruiting |
Toulouse, France | |
Contact: MAZEREEUW-HAUTIER Juliette | |
TOURS | Recruiting |
Tours, France | |
Contact: MARUANI Annabel | |
NANCY | Not yet recruiting |
Vandoeuvre les nancy, France | |
Contact: BURSZTEJN Anne-Claire |
Tracking Information | |||||||||
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First Submitted Date ICMJE | May 24, 2019 | ||||||||
First Posted Date ICMJE | June 3, 2019 | ||||||||
Last Update Posted Date | November 4, 2020 | ||||||||
Actual Study Start Date ICMJE | June 5, 2019 | ||||||||
Estimated Primary Completion Date | September 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Efficacy of a 12-week application period of 0.1% topical sirolimus in cutaneous microcystic lymphatic malformation versus topical vehicle [ Time Frame: Week 12 ] PGA (Physician Global Assessment) score assessed by the investigator physician (blinded from the treatment). PGA score ranges from 0 (clear) to 5 (severe lesions), and is commonly used in several dermatologic conditions. For each patient, PGA of the area treated with the intervention (0.1% topical sirolimus) will be compared to PGA of the area treated with topical vehicle (inactive comparator)
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Topical Sirolimus in Cutaneous Lymphatic Malformations | ||||||||
Official Title ICMJE | 0.1% Topical Sirolimus in the Treatment of Cutaneous Microcystic Lymphatic Malformations in Children and Adults: Phase II, Split-body Randomized, Double-blind, Vehicle-controlled Clinical Trial | ||||||||
Brief Summary | Cutaneous microcystic lymphatic malformations (CMLMs) are rare conditions of children and adults resulting from abnormal embryologic development of lymphatic vessels. They present as clusters of vesicles full of lymph and blood of various extent. They ooze and bleed, inducing maceration, esthetic impairment, scars, pain, bacterial infections and impaired quality of life. Currently, treatments for CMLMs are disappointing, and their management is challenging. Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine/threonine protein kinase involved in cell growth and proliferation, cellular metabolism, autophagy and angio-lymphangiogenesis. Topical sirolimus, known to be efficient and well tolerated in cutaneous angiofibromas linked to tuberous sclerosis, has recently been reported effective in few reports of patients with CMLMs. The objective of this trial is to compare the efficacy and safety of a 12-week application of 0.1% topical sirolimus versus topical vehicle in CMLMs in children and adults. | ||||||||
Detailed Description |
This blinded multicentre split body randomized controlled phase 2 trial aims to include 50 patients ≥ 6 years old who have a primary CMLM without an underlying malformation. The CMLM will be divided into 2 equal areas of the same severity that will be randomly allocated to 0.1% topical sirolimus or topical vehicle for 12 weeks. During the double-blind 12-week period, both topical products will be applied by a nurse to avoid inter-group contamination and for better compliance. At the end of the 12-week period, the patient/parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for 8 more weeks. Patients will also be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Split-body randomised, double-blind, vehicle-controlled clinical trial Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Patients, parents, nurses and investigators will be blinded for the treatment allocated to each area of the CMLM, during the first step of the study (until week 12, where primary endpoint will be assessed). To ensure the double blinding, both areas will be randomized, and the topical treatments (sirolimus and vehicle) to be applied will have similar packaging. Their appearance is similar, thus the active drug (topical sirolimus) and vehicle cannot be distinguished at drug allocation. Furthermore, the consistency of the creams is similar. Primary Purpose: Treatment
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Leducq S, Caille A, Barbarot S, Bénéton N, Bessis D, Boccara O, Bursztejn AC, Chiaverini C, Dompmartin A, Droitcourt C, Gissot V, Goga D, Guibaud L, Herbreteau D, Le Touze A, Léauté-Labrèze C, Lorette G, Mallet S, Martin L, Mazereeuw-Hautier J, Phan A, Plantin P, Quéré I, Vabres P, Bourgoin H, Giraudeau B, Maruani A; Groupe de Recherche de la Société Française de Dermatologie Pédiatrique. Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial. Trials. 2019 Dec 17;20(1):739. doi: 10.1186/s13063-019-3767-8. | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
55 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | June 2022 | ||||||||
Estimated Primary Completion Date | September 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 6 Years and older (Child, Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | France | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03972592 | ||||||||
Other Study ID Numbers ICMJE | PHRN17-AM / TOPICAL (DR180115) 2018-001359-11 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | University Hospital, Tours | ||||||||
Study Sponsor ICMJE | University Hospital, Tours | ||||||||
Collaborators ICMJE | University Hospital, Angers | ||||||||
Investigators ICMJE | Not Provided | ||||||||
PRS Account | University Hospital, Tours | ||||||||
Verification Date | October 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |