Clinical trial NCT04924608: Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Neurofibromatosis 1
Plexiform Neurofibroma (PN)
Keywords: Neurofibromatosis Type 1
NF1
Plexiform Neurofibroma (PN)
PNs
Selumetinib
MEK inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-06-14
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) for Arm A versus Arm B
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire
timeFrame: Approximately 3 years
measure: Duration of response (DoR) for Arm A
timeFrame: Approximately 3 years
measure: Progression Free Survival (PFS) for Arm A
timeFrame: Approximately 3 years
measure: Time to progression (TTP) for Arm A
timeFrame: Approximately 3 years
measure: Time to Response (TTR) for Arm A
timeFrame: Approximately 3 years
measure: Target PN volume for Arm A vs Arm B
timeFrame: Approximately 3 years
measure: Physical functioning assessed using PROMIS physical function items
timeFrame: Approximately 3 years
measure: Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL
timeFrame: Approximately 3 years
Other outcomes:
measure: Safety and tolerability of selumetinib as assessed by number and grade of adverse events
timeFrame: Approximately 3 years
measure: Pharmacokinetics (PK) of selumetinib for exposure-response analyses
timeFrame: Approximately 3 years
Locations:
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Rockville
country: United States
facility: Research Site
state: Maryland
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Commack
country: United States
facility: Research Site
state: New York
city: Melbourne
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Créteil
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Toulouse Cedex 09
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: National Cancer Institute (NCI)
name: Alice P. Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: