Evaluating the safety and efficacy of Trametinib in Arterio-Venous Malformations that are refractory to standard care
- Conditions
- Arteriovenous Malformations that are refractory to standard treatments or for which standard treatment are contra-indicatedTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2019-003573-26-BE
- Lead Sponsor
- Cliniques universitaires Saint-Luc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 20
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:
oTotal 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)
oSerum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN (or < 5.0 x ULN if hepatic metastases are present)
oSerum creatinine < 1.5 x ULN. If the serum creatinine is = 1.5 x ULN, then a 24-hour Creatinine Clearance must be conducted and the result must be = 60 mL/min.
4.Karnofsky score > 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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method