Treatment of symptomatic plexiform neurofibromas, a benign tumour associated with the disorder Neurofibromatosis type 1, in children with the drug trametinib

• Register: EUCTR
• Last refreshed on: 13 November 2023
• Main ID: EUCTR2018-001846-32-SE
• Date of registration: 31/07/2018
• Prospective Registration: Yes
• Primary sponsor: VO Barnmedicin, Skånes University Hospital
• Public title: Treatment of symptomatic plexiform neurofibromas, a benign tumour associated with the disorder Neurofibromatosis type 1, in children with the drug trametinib
• Scientific title: Treatment of NF1-related plexiform neurofibroma with trametinib; a single arm, open-label trial with the goals of volumetric partial remission and pain relief - plexifpc
• Date of first enrolment: 18/09/2018
• Target sample size: 15
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-001846-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Sweden

Contacts

• Name: AVD 63 / Björn Sigurdsson
• Affiliation: VO barnmedicin, Skånes University Hospital, Lund

• Name: AVD 63 / Björn Sigurdsson
• Affiliation: VO barnmedicin, Skånes University Hospital, Lund

Key inclusion & exclusion 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:
• 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

NF1-related plexiform neurofibroma

Intervention(s)

Trade Name: Mekinist
Product Name: Mekinist
Pharmaceutical Form: Oral drops

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: month 18 (interim analysis) and month final analysis at month 30.

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

Main Objective: Remission of NF1-related plexiform neurofibroma (PN)

Secondary Outcome(s)

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.

Secondary ID(s)

BUS2018-1

Source(s) of Monetary Support

Novartis Sverige AB

Ethics review

Status: Approved
Approval date: 14/08/2018
Contact: