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

Neurofibromatosis 1 Clinical Trial

— KOMET  

Official title:

A Phase III, Multicentre, International Study With a Parallel, Randomised, Double-blind, Placebo-controlled, 2 Arm Design to Assess the Efficacy and Safety of Selumetinib in Adult Participants With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas (KOMET)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04924608
• Other study ID #: D134BC00001
• Secondary ID: 2020-005607-39
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 19, 2021
• Est. completion date: March 17, 2025

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 146
• Est. completion date: March 17, 2025
• Est. primary completion date: August 5, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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 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

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1

Intervention

Drug:
• Selumetinib
Selumetinib oral capsules (10 mg and 25 mg)

Other:
• Placebo
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)

Locations

Country	Name	City	State
Australia	Research Site	Melbourne
Australia	Research Site	St Leonards
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	São Paulo
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Guangzhou
China	Research Site	Shenyang
France	Research Site	Creteil
France	Research Site	Lyon
France	Research Site	Toulouse Cedex 09
Germany	Research Site	Hamburg
Germany	Research Site	Tübingen
Germany	Research Site	Würzburg
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Roma
Japan	Research Site	Minato-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Shinjuku-ku
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Spain	Research Site	Badalona
Spain	Research Site	Madrid
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Commack	New York
United States	Research Site	Gainesville	Florida
United States	Research Site	Rockville	Maryland
United States	Research Site	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  France,  Germany,  Italy,  Japan,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety and tolerability of selumetinib as assessed by number and grade of adverse events	Adverse events are defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Approximately 3 years
Other	Pharmacokinetics (PK) of selumetinib for exposure-response analyses	Selumetinib and N-desmethyl selumetinib plasma concentrations assessment	Approximately 3 years
Primary	Confirmed Objective Response Rate (ORR) for Arm A versus Arm B	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	Approximately 3 years
Secondary	Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire	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	Approximately 3 years
Secondary	Duration of response (DoR) for Arm A	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	Approximately 3 years
Secondary	Progression Free Survival (PFS) for Arm A	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	Approximately 3 years
Secondary	Time to progression (TTP) for Arm A	TTP is defined as the time from the date of first selumetinib dose until date of disease progression by ICR per REiNS criteria	Approximately 3 years
Secondary	Time to Response (TTR) for Arm A	TTR is defined as the time from date of first selumetinib dose until the date of objective response by ICR per REiNS criteria	Approximately 3 years
Secondary	Target PN volume for Arm A vs Arm B	Difference in best percentage change from baseline in target PN volume by ICR per REiNS criteria	Approximately 3 years
Secondary	Physical functioning assessed using PROMIS physical function items	Difference in change from baseline between Arm A and Arm B	Approximately 3 years
Secondary	Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL	Difference in change from baseline between Arm A and Arm B	Approximately 3 years