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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04924608




Registration number
NCT04924608
Ethics application status
Date submitted
14/05/2021
Date registered
14/06/2021
Date last updated
25/06/2024

Titles & IDs
Public title
Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
Scientific 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)
Secondary ID [1] 0 0
2020-005607-39
Secondary ID [2] 0 0
D134BC00001
Universal Trial Number (UTN)
Trial acronym
KOMET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurofibromatosis 1 0 0
Plexiform Neurofibroma (PN) 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Skin 0 0 0 0
Dermatological conditions
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Selumetinib
Other interventions - Placebo

Experimental: Arm A - Selumetinib

Placebo comparator: Arm B - Placebo


Treatment: Drugs: Selumetinib
Selumetinib oral capsules (10 mg and 25 mg)

Other interventions: Placebo
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Confirmed Objective Response Rate (ORR) for Arm A versus Arm B
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [1] 0 0
Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
Duration of response (DoR) for Arm A
Timepoint [2] 0 0
Approximately 3 years
Secondary outcome [3] 0 0
Progression Free Survival (PFS) for Arm A
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
Time to progression (TTP) for Arm A
Timepoint [4] 0 0
Approximately 3 years
Secondary outcome [5] 0 0
Time to Response (TTR) for Arm A
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [6] 0 0
Target PN volume for Arm A vs Arm B
Timepoint [6] 0 0
Approximately 3 years
Secondary outcome [7] 0 0
Physical functioning assessed using PROMIS physical function items
Timepoint [7] 0 0
Approximately 3 years
Secondary outcome [8] 0 0
Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL
Timepoint [8] 0 0
Approximately 3 years

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
17/03/2025
Actual
Sample size
Target
Accrual to date
Final
146
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment hospital [2] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
Brazil
State/province [5] 0 0
Porto Alegre
Country [6] 0 0
Brazil
State/province [6] 0 0
Ribeirão Preto
Country [7] 0 0
Brazil
State/province [7] 0 0
São Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
China
State/province [10] 0 0
Beijing
Country [11] 0 0
China
State/province [11] 0 0
Guangzhou
Country [12] 0 0
China
State/province [12] 0 0
Shenyang
Country [13] 0 0
France
State/province [13] 0 0
Creteil
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Toulouse Cedex 09
Country [16] 0 0
Germany
State/province [16] 0 0
Hamburg
Country [17] 0 0
Germany
State/province [17] 0 0
Tübingen
Country [18] 0 0
Germany
State/province [18] 0 0
Würzburg
Country [19] 0 0
Italy
State/province [19] 0 0
Milano
Country [20] 0 0
Italy
State/province [20] 0 0
Napoli
Country [21] 0 0
Italy
State/province [21] 0 0
Roma
Country [22] 0 0
Japan
State/province [22] 0 0
Minato-ku
Country [23] 0 0
Japan
State/province [23] 0 0
Nagoya-shi
Country [24] 0 0
Japan
State/province [24] 0 0
Shinjuku-ku
Country [25] 0 0
Poland
State/province [25] 0 0
Bydgoszcz
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Moscow
Country [27] 0 0
Spain
State/province [27] 0 0
Badalona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
A global study to demonstrate the effectiveness of selumetinib in participants with NF1 who have symptomatic, inoperable plexiform neurofibromas.
Trial website
https://clinicaltrials.gov/study/NCT04924608
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alice P. Chen, MD
Address 0 0
National Cancer Institute (NCI)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04924608