Sirolimus for Cervicofacial lymphatic malformation | Cystic lymphangioma

Inclusion criteria

• {"criterion_text":"- Minor patients aged between 1 and 18 years, regardless of sex, with a cervico-facial lymphatic malformation of micro-cystic or mixed form with a unilateral or bilateral supra-hyoid location (class II, III and IV of the De Serres classification), or any form with mediastinal extension.\n- Presenting a chronic algic symptomatology, or functional symptomatology with respiratory discomfort or swallowing or phonatory disorders with a CDS score strictly below 8\n- For which curative treatment is not possible or presents a major functional or vital risk. Lesions corresponding to these definitions include extensions - exceeding half of the mobile hemi-tongue or half of the hemi-base of the tongue -infiltrating more than a third of the floor of the mouth -more than half of the jugal mucosa one-third of the hemipharynx -the larynx -the trachea -both recurrent spaces -the mediastinum -the infra-temporal fossa -the pterygoid muscles -the mandibular or maxillary bone intrastructures -conjunctivo-palpebral -intra-conical orbital structures\n- Karnofsky score (>10 years) or Lansky score (≤10 years) >50%\n- Biological functions with the following standards: -Neutrophil count ≥1.0 x 109/L -Platelet count ≥ 100 x 109/L -Haemoglobin ≥ 8 g/dL -Total bilirubin ≤ 1.5 ULN -Transaminases < 2.5 ULN -Serum albumin ≥ 2 g/dL. -LDL cholesterol <160 mg/dL -Triglycerides < 150 mg/dL -Glomerular filtration rate (GFR) calculated using the Schwartz formula (for creatinine expressed in mg/l): GFR (ml/min/1.73 m2) = [k x height (cm)] / [creatinine (mg/l) x 8.84] > 70 ml/min/1.73 m2 With : k = 29 for premature newborns k = 40 for full-term newborns and children under 1 year of age k = 49 for children aged 2 to 12 years k = 49 for girls aged 13 to 21 k = 62 for boys aged 13 to 21\n- Informed consent signed by both parents or the person(s) with parental authority\n- Negative pregnancy test if indicated\n- Person covered by a Social Security system\n- For patients who have undergone surgery or sclerotherapy: inclusion possible if they meet the above criteria and after a minimum of 2 months after the procedure. Surgical procedures that do not modify the target area, such as tracheostomy or gastrostomy, do not modify the inclusion delay"}

Exclusion criteria

• {"criterion_text":"- Non-compliance with inclusion criteria\n- Known allergy to peanuts or soya\n- Inability to receive enlightened information\n- Not covered by the social security system\n- Refusal to sign the consent form\n- For patients of childbearing potential, contraception other than oral contraceptives should be offered during treatment. Although the results of a single-dose interaction study with an oral contraceptive suggest the absence of a pharmacokinetic interaction, the possibility of pharmacokinetic changes that may affect the efficacy of oral contraception during prolonged treatment with Rapamune® cannot be ruled out.\n- Pregnancy or breastfeeding\n- Patients, parents or legal guardians incapable of giving consent or benefiting from a legal protection regime (guardianship)\n- Refusal of the child to participate\n- Other immunosuppressive treatment or long-term general corticosteroid therapy\n- Chronic renal failure\n- Chronic liver failure\n- Digestive disorders that may interfere with the absorption of Rapamycin: ulcerative gastritis, repeated vomiting, malabsorption syndrome, etc.\n- Severe uncontrolled infection\n- Patients requiring treatment that may induce CYP3A4 activity (rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin) or inhibit CYP3A4 activity (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin, diltiazem, verapamil, nicardipine ; clotrimazole, fluconazole , troleandomycin , bromocriptine, cimetidine, danazol , protease inhibitors) due to changes in Rapamycin metabolism and consequent changes in Rapamycin plasma levels.\n- Patients already receiving treatment with an inhibitor of the mTOR pathway\n- Patients taking digestive motor stimulants such as cisapride and metoclopramide if they cannot be stopped since Pharmacokinetic interactions may be observed."}

Primary endpoints

• {"endpoint_text":"- Assessment of the response in terms of lesion volume using volumetric MRI 3 months after the therapeutic plateau has been reached. A transient increase in lesion volume may be observed in the case of locoregional infections or direct trauma. In these situations, MRI may be delayed by one or two weeks to allow treatment of the intercurrent problem. A decrease in volume ≥ 1/5th will be considered a positive response.","definition_or_measurement_approach":"Volumetric MRI performed 3 months after reaching therapeutic plateau; a decrease in lesion volume ≥ 1/5th (≥20%) is considered a positive response. MRI may be delayed by 1-2 weeks in case of infection or trauma."}

Secondary endpoints

• {"endpoint_text":"- The kinetics of the response are assessed by MRI at 6 months and 1 year, in order to evaluate the evolution at the end of treatment and at 6 months after stopping treatment.","definition_or_measurement_approach":"MRI at 6 months and 12 months to assess response kinetics, evaluating evolution at end of treatment and at 6 months after treatment cessation."}
• {"endpoint_text":"- Known adverse reactions will be systematically investigated on a monthly basis.","definition_or_measurement_approach":"Monthly safety surveillance for known adverse reactions (NCI-CTC 3.0 scale)."}
• {"endpoint_text":"- Clinical evaluation of the extent of the lesion, with photographic and video recording of the pharyngolaryngeal fibroscopy, with assessment of the infiltrated areas, the macroscopic appearance and the haemorrhagic appearance of the lesions.","definition_or_measurement_approach":"Clinical assessments including photography and video of pharyngolaryngeal fibroscopy to document infiltrated areas, macroscopic and haemorrhagic appearance."}
• {"endpoint_text":"- The scoring used the same scores as those used for the initial assessment, even if the patient changed age group during the study. This clinical assessment was carried out at 3 months, 6 months and 12 months. The assessment criterion is based on the change in scores between each examination.","definition_or_measurement_approach":"Clinical scoring at 3, 6 and 12 months using the same baseline scores; endpoint based on change in scores between examinations."}
• {"endpoint_text":"- To evaluate the effectiveness of mTOR pathway inhibition, we will assess the impact of Rapamycin on signaling proteins (pAKT, p70S6 kinase, pMEK, pERK) in cellular samples before and after treatment using Bioplex, a method for analyzing phosphorylated proteins. We will also measure circulating angiogenic factors (VEGF C, VEGFR3) in serum samples before and after treatment using ELISA.","definition_or_measurement_approach":"Biological assays: Bioplex analysis of phosphorylated signaling proteins (pAKT, p70S6K, pMEK, pERK) in cellular samples pre- and post-treatment; ELISA measurement of circulating angiogenic factors (VEGF C, VEGFR3) in serum pre- and post-treatment."}

France

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

21-11-2024

Processing Time Days

35

Number Of Sites

8

Number Of Participants

28

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Lille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France