NF1-related plexiform neurofibroma
Conditions
Interventions
Trade Name: Mekinist
Product Name: Mekinist
Pharmaceutical Form: Oral drops
Sponsors
VO Barnmedicin, Skånes University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: NF1-related PN with severe - or with high suspicion of threatening - manifestations • Informed consent given • Age 1:0-17:11 Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • NF1-related PN does not fulfill characteristics for acceptable volumetric MRI assessments as outlined in box Criterion for volumetric assessment. • Lactating or pregnant or sexual active females, who do not use safe contraception. Sexual active males who do not use condom. • History of other malignancies than classic NF1-related WHO grade 1 tumor (i.e. PN or optic pathway glioma). • Subjects with a history of NF-1 related cerebral vascular anomaly (such as Moyamoya). • Subjects with NF-1, receiving pharmaceutical therapy for optic pathway malignancy/ies. • Any medication for treatment of left ventricular systolic dysfunction. • Administration of an investigational study treatment within 30 days preceding the first dose of the study treatment in this study. • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatment or excipients that contraindicate their participation. • Current active liver or biliary disease • History of hepatic sinusoid obstructive syndrome (venoocculsive disease) within the prior 3 months. • History of heparin-induced thrombocytopenia. • History of interstitial lung disease or pneumonitis. • History of or current evidence of retinal vein occlusion (RVO). • A history of known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection may be enrolled. • Presence of condition that will interfere significantly with the absorption of drugs. • Evidence of cardiovascular risk, LVEF below LLN, Qtc >480 millisecond, clinical significant uncontrolled arrhythmia, congestive heart failure, acute coronary syndrome or history thereof.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Remission of NF1-related plexiform neurofibroma (PN);Secondary Objective: Reversal of clinical symptoms of NF1-related PN Exploratory: Evaluate changes in cognitive performance;Primary end point(s): Remission of tumor volume =20% evaluated with volumetric MRI;Timepoint(s) of evaluation of this end point: month 18 (interim analysis) and month final analysis at month 30. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Reversal of clinical symptoms of NF1-related PN. Evaluated with pain diary, VAS scale or Faces Pain Scale, from month 0 to 30 following. Descriptive. Exploratory: Change of either; full scale IQ or primary indexes (WISC V), Learning and Memory functions and visuospatial functions (selected test from NEPSY II), or attention (Conners CPT3); with p-value <0.05;Timepoint(s) of evaluation of this end point: month 18 (interim analysis) and month final analysis at month 30 for pain and after month 18 for cognitive function. | — |
Countries
Sweden
Contacts
Public ContactAVD 63 / Björn Sigurdsson
VO barnmedicin, Skånes University Hospital, Lund
Outcome results
None listed