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Vascular MalformationsPhase 2TOPICALNCT03972592

Topical Sirolimus in Cutaneous Lymphatic Malformations

A Phase 2 study testing Topical 0.1% Sirolimus in people with Vascular Malformations and Lymphatic Malformation, run by University Hospital, Tours at 17 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 years and older
What is being tested?
Topical 0.1% Sirolimus
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
55 participants
Where
17 sitesFrance
Study dates
5 Jun 2019to 14 Aug 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients ≥ 6 years
  • Updated immunization schedule
  • Diagnosis of primary cutaneous microcystic lymphatic malformation (CMLM) confirmed by histopathological or dermoscopic examination, with or without an underlying malformation or a syndromic malformation (Protée syndrome for instance), responsible for impairment (oozing, bleeding and/or pain)
  • CMLM ≥ 20 cm2, that can be divided into 2 parts of similar severity
  • Informed, written consent of the subject and his/her parents if < 18 years
  • Rights to French social security (including CMU)

Who cannot join

  • Patients with lymphatic malformation requiring a continued background therapy (involving deep organs)
  • Secondary lymphatic malformations (lymphangiectasia post-radiotherapy, etc)
  • Previous treatment with oral or topical mTOR inhibitors within 12 months before inclusion
  • Previous treatment with oral or topical steroids within 10 days before inclusion
  • Immunosuppression (immunosuppressive disease or immunosuppressive treatment)
  • Ongoing neoplasia
Show all 13Show fewer
  • Active chronic infectious disease (Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus, etc)
  • Local fungal, viral (Herpes Simplex Virus, Varicella Zoster Virus, etc) or bacterial infection on the site of the CMLM (based on clinical examination)
  • Skin necrosis
  • Known allergy to one of the components of the topical sirolimus preparation or vehicle
  • Women of child-bearing potential (including teenagers) not using a reliable contraceptive method until the end of the study
  • Pregnant or breastfeeding women
  • Subject already involved in another therapeutic trial

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

France17 sites

  • ANGERS

    Angers

  • BORDEAUX

    Bordeaux

  • LYON AD

    Bron

  • LYON PED

    Bron

  • CAEN

    Caen

  • DIJON

    Dijon

  • Marseille

    Marseille

  • Montpellier

    Montpellier

  • NANTES

    Nantes

  • NICE

    Nice

  • Lariboisiere

    Paris

  • NECKER

    Paris

  • QUIMPER

    Quimper

  • RENNES

    Rennes

  • TOULOUSE

    Toulouse

  • TOURS

    Tours

  • NANCY

    Vandœuvre-lès-Nancy

Other trials in France

About this study

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

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.

Read the 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.

Being tested
Topical 0.1% Sirolimus, Topical Vehicle
Keywords
Cutaneous Microcystic Lymphatic Malformations
Medical subject headings
Vascular Malformations, Lymphatic Abnormalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Topical 0.1% SirolimusDrug

    Also called Verum

    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.

  • Topical VehicleDrug

    Also called Placebo

    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.

Study groups in NCT03972592
Study groupRoleWhat they receive
Topical sirolimusExperimentalThe 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.
Receives: Drug: Topical 0.1% Sirolimus
VehiclePlacebo comparatorThe 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.
Receives: Drug: Topical Vehicle

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of a 12-week application period of 0.1% topical sirolimus in cutaneous microcystic lymphatic malformation versus topical vehicle

    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)

    Measured: Week 12

Secondary outcomes (10)

  1. Efficacy of 0.1% topical sirolimus in cutaneous microcystic lymphatic malformation versus topical vehicle

    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)

    Measured: Day 1, Week 6, Week 20, Month 12

  2. Efficacy of 0.1% topical sirolimus vs vehicle regarding each of the following complications of the CMLM: oozing, bleeding, erythema, and thickness

    Assessment by the investigator blinded to treatment with a visual analog scale (VAS) from 0 to 10 (0: no improvement, 10: recovery)

    Measured: Day 1, Week 12, Week 20, Month 12

  3. Number of independent experts who correctly identify which area among both received the active treatment for each patient on the basis of standardised photographs

    Standardized photographs will be performed at baseline and week 12: the experts will have to identify, at the end of the study, which area among both received the active treatment. In case of disagreement, a consensus will be reached between both experts; if consensus is not reached, a third expert will be sought for final decision. Interpretation by dermatologic experts (i.e correct identification of intervention/vehicle treated area) will be considered as correct or false, and the proportion of correct interpretation will be estimated. The proportion of correct interpretation will be compared to the theoretical 50% value, corresponding to a random assessment. Five photographs will be taken: 1) one of the patient including the malformation 2) one of the malformation (distance of 50 cm), 3) one of the malformation (distance of 15 cm), 4) profile photography and finally 5) three quarter view.

    Measured: Day1, Week 12

  4. Global self-reported efficacy of topical sirolimus vs vehicle (with help of parents in case of children under 16 years)

    Self-assessment of the global improvement of CMLM in both areas using a VAS (Visual Analog Scale) from 0 to 10 (0 no improvement and 10 recovery)

    Measured: Week 12, Week 20, Month 12

  5. Functional and esthetic impairments (self-reported with help of parents in case of children under 16 years)

    Using a VAS (Visual Analog Scale) from 0 to 10 (0 no improvement and 10 recovery)

    Measured: Day1, Week 20, Month 12

  6. Pain linked to the CMLM (with help of parents in case of children under 16 years)

    Using a VAS (Visual Analog Scale) from 0 to 10 (0 no pain and 10 worst imaginable pain)

    Measured: Day1, Week 20, Month 12

  7. Effect on quality of life

    Self-assessment of quality of life using the validated DLQI (Dermatology Life Quality Index) scale, or Child-DLQI for children (equal ou under 16 years old) from 0 to 30 (0 no impact on quality of life and 30 maximum impact on quality of life)

    Measured: Day 1, Week 20, Month 12

  8. Evaluation of systemic passage of sirolimus by dosage of serum level of sirolimus

    Dosage of serum level of sirolimus

    Measured: Week 6, Week 12, Week 20, +/- Week 16 (if CMLM ≥ 30*30 cm and/or ≥900 cm2)

  9. Number of patients with biological adverse events and total number of biological adverse events (to assess the biological tolerance of topical sirolimus)

    Number of patients with biological adverse events and total number of biological adverse events (blood samples at baseline, week 12 and week 20)

    Measured: Baseline, Week 12, Week 20

  10. Number of patients with clinical adverse events and total number of clinical adverse events (to assess the clinical tolerance of topical sirolimus)

    Number of patients with clinical adverse events and total number of clinical adverse events (record of local and general adverse events)

    Measured: Week 6, Week 12, Week 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2019
  2. Study start5 Jun 2019
  3. Primary completion14 Aug 2024
  4. Study completion14 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Split-body randomised, double-blind, vehicle-controlled clinical trial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03972592
Sponsor's protocol ID
PHRN17-AM / TOPICAL (DR180115)
Other IDs
2018-001359-11, 2018
Acronym
TOPICAL
Status last verified
Feb 2026
First submitted
24 May 2019
Last updated
13 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Leducq S, Caille A, Barbarot S, Beneton N, Bessis D, Boccara O, Bursztejn AC, Chiaverini C, Dompmartin A, Droitcourt C, Gissot V, Goga D, Guibaud L, Herbreteau D, Le Touze A, Leaute-Labreze C, Lorette G, Mallet S, Martin L, Mazereeuw-Hautier J, Phan A, Plantin P, Quere I, Vabres P, Bourgoin H, Giraudeau B, Maruani A; Groupe de Recherche de la Societe Francaise de Dermatologie Pediatrique. 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.

    PubMed 31847908

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Topical 0.1% Sirolimus in people with Vascular Malformations and Lymphatic Malformation, run by University Hospital, Tours at 17 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of a 12-week application period of 0.1% topical sirolimus in cutaneous microcystic lymphatic malformation versus topical vehicle (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03972592, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.

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