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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04924608
Ethics application status
Date submitted
14/05/2021
Date registered
14/06/2021
Date last updated
20/09/2021

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 - 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
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 - 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
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Approximately 3 years
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Approximately 3 years
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Approximately 3 years
Secondary outcome [7] 0 0
Physical functioning assessed using PROMIS physical function items - Difference in change from baseline between Arm A and Arm B
Timepoint [7] 0 0
Approximately 3 years
Secondary outcome [8] 0 0
Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL - Difference in change from baseline between Arm A and Arm B
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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Confirmed or suspected malignant glioma or MPNST (optic glioma not requiring
chemotherapy 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Brazil
State/province [12] 0 0
Porto Alegre
Country [13] 0 0
Brazil
State/province [13] 0 0
Ribeirão Preto
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Germany
State/province [17] 0 0
Hamburg
Country [18] 0 0
Germany
State/province [18] 0 0
Tübingen
Country [19] 0 0
Germany
State/province [19] 0 0
Würzburg
Country [20] 0 0
Italy
State/province [20] 0 0
Milano
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
Netherlands
State/province [25] 0 0
Rotterdam
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Moscow
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
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 Corp.
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/show/NCT04924608
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Geraldine O'Sullivan Coyne, MD PhD
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
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

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