TOPical Sirolimus in linGUal Microcystic Lymphatic Malformation -TOPGUN (TOPGUN)
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|ClinicalTrials.gov Identifier: NCT04128722|
Recruitment Status : Active, not recruiting
First Posted : October 16, 2019
Last Update Posted : January 23, 2020
Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations, presenting as clusters of cysts filled with lymph fluid or blood. They are responsible for a heavy burden even with small well-limited lesions because of oozing, bleeding, infections, or even speech, chewing or breathing impairment. Pain and aesthetic prejudice are also frequently reported. The natural history of LMLMs is progressive worsening. LMLMs complex management requires multidisciplinary care in specialised centres, and the "wait-and-see" approach is frequently used. In complicated lymphatic malformations, whatever the location, treatment with oral sirolimus, an mTOR (mammalian Target of Rapamycin) inhibitor, is often used.
Topical sirolimus is a known effective treatment for some cutaneous conditions such as angiofibromas in tuberous sclerosis. Topical applications of sirolimus on the buccal mucosae have been reported in erosive lichen planus and oral pemphigus vulgaris with good tolerance and none to slight detectable blood sirolimus concentrations.
The objective of this study is to evaluate the efficacy and safety of a 1mg/mL sirolimus solution applied once daily on mild to moderate lingual microcystic lymphatic malformation in children and adults after 4, 8, 12, 16, 20 and 24 weeks of treatment as compared to usual care (no treatment).
|Condition or disease||Intervention/treatment||Phase|
|Lingual Microcystic Lymphatic Malformations||Drug: Sirolimus Oral Liquid Product 1mg/mL||Phase 2|
This is a randomized, open-labelled, multicenter pilot study using an individually randomized stepped wedge design over a 24 weeks period to evaluate topical application of 1 mg/mL sirolimus solution, 0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation that do not require systemic treatment, the experimental intervention versus usual care (no treatment), the control condition.
In this design, subjects are included in a cohort where at a randomized time (W0, W4, W8 or W12), they switch from an observational period to the interventional period.
All subjects will be followed for 24 weeks
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Individually randomized stepped wedge|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||Primary outcome is assessed on anonymised photographs by an adjudication committee blinded from treatment allocation|
|Official Title:||TOPical Sirolimus in linGUal Microcystic Lymphatic Malformation -TOPGUN|
|Actual Study Start Date :||November 30, 2019|
|Estimated Primary Completion Date :||January 31, 2021|
|Estimated Study Completion Date :||April 28, 2021|
Experimental: Sirolimus 1mg/mL
Application of 1 mg/mL sirolimus solution, 0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation, the experimental intervention versus usual care (no treatment), the control condition.
Drug: Sirolimus Oral Liquid Product 1mg/mL
0.5 mL to 1 mL according to the size of the lesion, once daily, on lingual microcystic lymphatic malformation
Other Name: Experimental treatment
No Intervention: Control condition
Usual care, i.e. no intervention
- Change in Physical Global Assessment (PGA) after topical application of Sirolimus for 12 weeks [ Time Frame: 12 weeks ]
The primary outcome will consist in the evaluation of global severity of the LMLM using PGA (Physical Global Assessment) 0 to 5 score, by three independent blinded experts, on monthly standardized photographs.
A 1-point improvement versus baseline in PGA scale would already have a clinical relevance.
Our primary analysis will focus on change in PGA after topical application of Sirolimus for 12 weeks
- Investigator-assessed PGA [ Time Frame: at weeks 0, 4, 8, 12, 16, 20 and 24 ]Investigator-assessed PGA (Physical Global Assessment)
- Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort, [ Time Frame: at weeks 0, 4, 8, 12, 16, 20 and 24. ]Assessment by the patient regarding severity of oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain and global discomfort, each using a numeric scale from 0 to 10 (0: clear, 10: very severe), at weeks 0, 4, 8, 12, 16, 20 and 24
- Global evolution assessed by the patient [ Time Frame: at weeks 4, 8, 12, 16, 20 and 24. ]Global evolution assessed by the patient from -10 to 10 (-10 = severe worsening, 0 = no change, 10 = complete recovery), at weeks 4, 8, 12, 16, 20 and 24.
- Global Quality of life assessment [ Time Frame: at baseline, at time of switch to the intervention (either week 0, week 4, week 8 or week 12) and week 24. ](DLQI or children's DLQI for minors aged 5 to 16), at baseline, time of switch to treatment and week 24.
- Measurements of the lesion [ Time Frame: at baseline, at time of switch to the intervention (either week 0, week 4, week 8 or week 12) and week 24. ]by the investigator, at baseline, time of switch to treatment and week 24.
- Time to obtain optimal results [ Time Frame: up to 24 weeks ]i.e. time from switch to treatment to time reaching the minimal PGA score
- Assessment of tolerance of topical sirolimus: [ Time Frame: from the switch to intervention up to the end of the study, i.e a maximum of 24 weeks. ]record of local side effects at each visit after the patient has crossed over to the intervention, up to 24 weeks
- General side effects [ Time Frame: rom the switch to intervention up to the end of the study, i.e a maximum of 24 weeks. ]Follow-up of general side effects
- Assessment of sirolimus blood passage [ Time Frame: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until week 24 ]by measuring residual sirolimus blood concentration: after 4 weeks of treatment, then 8 weeks, then every 8 weeks until week 24
- Evaluation of biological safety [ Time Frame: after 8,16 and up to 24 weeks ]Number of participants with at least one biological abnormality treatment-related adverse events as assessed by CTCAE v4.0
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04128722
|Univsersity of TOURS _ Service de Dermatologie|
|Tours, Indre Et Loire, France, 37044|
|REGIONAL Hospital of ORLEANS -Service de Dermatologie|
|Orléans, Loiret, France, 45000|
|Study Director:||Annabel MARUANI, MD-PHD||University Hospital of TOURS;INSERM 1246 SPHERE|