Treatment of NF1-related Plexiform Neurofibroma With Trametinib

Phase 2

Active, not recruiting

• Conditions: Child; Neurofibroma, Plexiform; Neurofibromatosis 1
• Interventions: Drug: Trametinib

• Registration Number: NCT03741101
• Lead Sponsor: Region Skane

Brief Summary

This trial, Treatment of NF1-related plexiform neurofibroma with trametinib; a single arm,open-label study with the goals of volumetric partial remission and pain relief (EudraCT 2018-001846-32, Sponsor protocol number BUS2018-1, related Novartis reference number CTMT212ASE01T) is a pediatric clinical trial that investigates the potential use of the drug trametinib (Mekinist®) as treatment for symptomatic or likely to become symptomatic NF1-related plexiform neurofibromas (PN) in children between 1 year and 17 year and 11 months of age.

Trametinib is orally administered qd at 0.025 mg/kg up to a maximum of 2 mg from six years of age and 0.032mg/kilo up to 5 years of age, provided either as tablets or as oral solution. It is manufactured and distributed by Novartis under the trade name Mekinist®.

The primary endpoint is remission of tumor volume ≥20%, evaluated using volumetric MRI at 18 and 30 months of treatment.

The secondary endpoint is reversal of pain from NF1-related PN, evaluated monthly with agespecific pain scales; VAS scale (from 8 years) or Faces Pain Scale (from 3 to 8 years).

As an exploratory measure, the potential effects of the treatment on the cognitive function will be assessed using well-established tests such as WISC-V (age range 6:0 - 16:11), NEPSY-II (age range 3:0-16:11), and CPT-3 (age range 8:0 - adult).

Cognitive dysfunction is well described in patients with NF1, and the MAPK/ERK-pathway has been indicated to be involved in cognition.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-11-05
• Study First Submitted QC: 2018-11-12
• Study First Posted: 2018-11-14
• Study Start: 2019-06-10
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-10
• Last Update Posted: 2024-04-11
• Primary Completion: 2024-07-15
• Study Completion: 2024-12-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm study	Trametinib	children treated with trametinib

Primary Outcome Measures

Name	Time	Method
Remission of tumor volume ≥20%	0 - 18 months	Interim analysis of pooled data at 18 months with volumetric mri of tumor volume versus volume at enrolment. This is an interim analysis of primary outcome and not primary analysis of primary outcome".

Secondary Outcome Measures

Name	Time	Method
Reversal of NF1-related PN elicited - VAS scale pain	0 - 30 months.	Evaluated with monthly VAS pain scale from 8 years at enrolment. Monthly. 0-10 point scale. Descriptive. Analysis of pooled data after month 30.
Reversal of NF1-related PN elicited pain - Faces Pain Scale	0 - 30 months.	Evaluated with monthly Faces Pain Scale from under 8 years at enrolment. Monthly. 0-10 scale. Descriptive. Analysis of pooled data after month 30.

Trial Locations

Locations (1)

Skåne University Hospital; 🇸🇪 Lund, Sweden