Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas

Phase 3

Active, not recruiting

• Conditions: Neurofibromatosis 1; Plexiform Neurofibroma (PN)
• Interventions: Other: Placebo; Drug: Selumetinib

• Registration Number: NCT04924608
• Lead Sponsor: AstraZeneca

Brief Summary

A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.

Detailed Description

This is a randomized, double-blind, placebo-controlled, 2 arm multicentre, global Phase III study to assess the efficacy and safety of selumetinib compared with placebo in adult participants with NF1 who have symptomatic, inoperable PN.

Study Timeline

• Study First Submitted: 2021-05-14
• Study First Submitted QC: 2021-06-07
• Study First Posted: 2021-06-14
• Study Start: 2021-11-19
• Primary Completion: 2024-08-05
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-09
• Study Completion: 2025-03-17

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 146

Inclusion Criteria

• Adults ≥ 18 years at enrollment with diagnosis of NF1 with symptomatic, inoperable PN
• At least one inoperable target PN measurable by volumetric MRI analysis
• Chronic target PN pain score documented for minimum period during screening period
• Stable chronic PN pain medication use at enrollment
• Adequate organ and marrow function

Key

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Exclusion Criteria

• Confirmed or suspected malignant glioma or MPNST (low grade glioma, including optic glioma not requiring systemic therapy or radiation therapy are exempt from this exclusion)
• History of malignancy except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence
• Clinically significant cardiovascular disease, including inherited coronary disease, acute coronary syndrome within 6 months prior to enrollment, uncontrolled angina, symptomatic heart failure, cardiomyopathy, severe valvular heart disease, abnormal LVEF and uncontrolled hypertension
• Ophthalmological findings/conditions including intraocular pressure > 21 mmHg, RPED/CSR or RVO
• Prior exposure to MEK inhibitors

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B	Placebo	Placebo
Arm A	Selumetinib	Selumetinib

Primary Outcome Measures

Name	Time	Method
Confirmed Objective Response Rate (ORR) for Arm A versus Arm B	Approximately 3 years	ORR will be defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria

Secondary Outcome Measures

Name	Time	Method
Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire	Approximately 3 years	Difference in mean change from baseline in chronic target PN pain intensity score between Arm A and Arm B, obtained using an NRS-11 scale to assess pain intensity of a target plexiform neurofibroma
Progression Free Survival (PFS) for Arm A	Approximately 3 years	PFS will be defined as the time from first selumetinib dose until date of disease progression by ICR per REiNS criteria or death due to any cause
Time to progression (TTP) for Arm A	Approximately 3 years	TTP is defined as the time from the date of first selumetinib dose until date of disease progression by ICR per REiNS criteria
Time to Response (TTR) for Arm A	Approximately 3 years	TTR is defined as the time from date of first selumetinib dose until the date of objective response by ICR per REiNS criteria
Target PN volume for Arm A vs Arm B	Approximately 3 years	Difference in best percentage change from baseline in target PN volume by ICR per REiNS criteria
Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL	Approximately 3 years	Difference in change from baseline between Arm A and Arm B
Duration of response (DoR) for Arm A	Approximately 3 years	DoR will be defined as the time from the date of first documented response (which is subsequently confirmed) until progression by ICR per REiNS criteria or death due to any cause
Physical functioning assessed using PROMIS physical function items	Approximately 3 years	Difference in change from baseline between Arm A and Arm B

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom