Arteriovenous Malformations that are refractory to standard treatments or for which standard treatment are contra-indicated
Conditions
Interventions
Trade Name: Mekinist
Product Name: Mekinist
Pharmaceutical Form: Coated tablet
Sponsors
Cliniques universitaires Saint-Luc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with complex and symptomatic fast-flow vascular malformations that are refractory to standard care such as medical treatment, surgical resection and/or embolization (ineffective or accompanied by major complications) or for wich standard care is contra-indicated. 2. Patients must have adequate bone marrow function: hemoglobine> 10,0 g/dl, neutrophils >1.500/mm³ and platelets > 100.000/mm³. 3. Patients must have the following laboratory values: o Total serum bilirubin = 1.5 x ULN (or totally bilirubin =3 x ULN with direct bilirubin = 1.5 x ULN in patients with well documented Gilbert Syndrome) o Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN (or 50 5. Negative urine pregnancy test in females with a childbearing potential. 6. Sexually active female patients (and female partners of male patients) must use adequate contraceptive measures while on study and for up to 8 weeks after ending treatment. Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. As AVM can result in impaired cardiac function, congestive heart failure is allowed if stabilized. New York Heart Association functional classification Grade 3-4 congestive heart failure should be excluded from this study, but remains at the discretion of the investigator as trametinib could indirectly improve cardiac function by controlling AVM. Other significant cardiac diseases, including unstable angina pectoris, ventricular arrhythmia, valvular disease with documented compromise in cardiac function, myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function, family history of congenital long or short QT, or known history of QT/QTc prolongation of Torsades de Pointes (TdP) are excluded from this trial. 2. Impairment of Gastro-Intestinal (GI) function or GI disease that may significantly alter the absorption of trametinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea = Grade 2, malabsorption syndrome, or small bowel resection) 3. Known hypersensitivity to drugs or metabolites from similar classes as study treatment. 4. Patient has (an)other concurrent severe and /or uncontrolled medical condition(s) that would, in the investigator’s judgement, contraindicate participation in the clinical study (e.g. acute or chronic pancreatitis, liver cirrhosis, active chronic hepatitis, severely impaired lung function with a spirometry = 50% of the normal predicted value and/or O2 saturation = 88% at rest, etc.) 5. Patient with history of Retinal pigment epithelial detachments or Retinal vein occlusion 6. Immunocompromised patients, including known seropositivity for HIV 7. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this clinical study is 1)to confirm the security of trametinib and long-term tolerability in patients with Arteriovenous Malformations (AVM) 2)to evaluate the efficacy of trametinib on signs and symptoms caused by AVMs that are refractory to standard care ? whether trametinib treatment can alleviate signs and symptoms caused by AVM ? whether trametinib could reduce volume of the malformation (on MRI) on a long-term follow-up ? whether patients will see their quality of life improved. ;Secondary Objective: Not applicable;Primary end point(s): All patients will be seen monthly for the first 3 months and then every three months, in order to evaluate the efficacy and safety of trametinib. Doppler ultrasonography and cardiac echography (Ventriculography) will be performed in baseline and at 6, 12 and 24 months; Magnetic Resonance Imaging (MRI) and arteriography will be performed at baseline, 12 and 24 months. ;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): At the end of 2 years, the treatment is interrupted and the patient is followed during 5 years. In case of resurgence of symptoms, trametinib could be restarted. ;Timepoint(s) of evaluation of this end point: 5 years | — |
Countries
Belgium
Contacts
Public ContactGuichet académique
CTC
Outcome results
None listed