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

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ClinicalTrials.gov Identifier: NCT04924608
Recruitment Status : Recruiting
First Posted : June 14, 2021
Last Update Posted : November 29, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Neurofibromatosis 1 Plexiform Neurofibroma (PN) Drug: Selumetinib Other: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 19, 2021
Estimated Primary Completion Date : October 24, 2024
Estimated Study Completion Date : May 22, 2025


Arm Intervention/treatment
Experimental: Arm A
Selumetinib
Drug: Selumetinib
Selumetinib oral capsules (10 mg and 25 mg)
Other Name: AZD6244

Placebo Comparator: Arm B
Placebo
Other: Placebo
Placebo oral capsules for Selumetinib masking (10 mg and 25 mg)




Primary Outcome Measures :
  1. Confirmed Objective Response Rate (ORR) for Arm A [ Time Frame: 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 :
  1. Change in chronic target PN pain intensity from baseline for Arm A versus Arm B as assessed using a PRO questionnaire [ Time Frame: 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

  2. Duration of response (DoR) for Arm A [ Time Frame: 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

  3. Progression Free Survival (PFS) for Arm A [ Time Frame: 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

  4. Time to progression (TTP) for Arm A [ Time Frame: 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

  5. Time to Response (TTR) for Arm A [ Time Frame: 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

  6. Target PN volume for Arm A vs Arm B [ Time Frame: Approximately 3 years ]
    Difference in best percentage change from baseline in target PN volume by ICR per REiNS criteria

  7. Physical functioning assessed using PROMIS physical function items [ Time Frame: Approximately 3 years ]
    Difference in change from baseline between Arm A and Arm B

  8. Health Related Quality of Life (HRQoL) outcomes assessed using PlexiQoL [ Time Frame: Approximately 3 years ]
    Difference in change from baseline between Arm A and Arm B


Other Outcome Measures:
  1. Safety and tolerability of selumetinib as assessed by number and grade of adverse events [ Time Frame: Approximately 3 years ]
    Adverse events are defined according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0

  2. Pharmacokinetics (PK) of selumetinib for exposure-response analyses [ Time Frame: Approximately 3 years ]
    Selumetinib and N-desmethyl selumetinib plasma concentrations assessment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04924608


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, Alabama
Research Site Withdrawn
Birmingham, Alabama, United States, 35294
United States, Florida
Research Site Not yet recruiting
Gainesville, Florida, United States, 32610
United States, Indiana
Research Site Withdrawn
Indianapolis, Indiana, United States, 46202
United States, Maryland
Research Site Not yet recruiting
Rockville, Maryland, United States, 20852
United States, Minnesota
Research Site Withdrawn
Rochester, Minnesota, United States, 55905
United States, Missouri
Research Site Not yet recruiting
Saint Louis, Missouri, United States, 63156
United States, New York
Research Site Not yet recruiting
Commack, New York, United States, 11725
Research Site Withdrawn
New York, New York, United States, 10016
United States, North Carolina
Research Site Withdrawn
Chapel Hill, North Carolina, United States, 27514
United States, Pennsylvania
Research Site Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
Research Site Not yet recruiting
Salt Lake City, Utah, United States, 84112
United States, Virginia
Research Site Not yet recruiting
Richmond, Virginia, United States, 23219
United States, Washington
Research Site Withdrawn
Seattle, Washington, United States, 98195
Australia
Research Site Recruiting
Melbourne, Australia, 3000
Research Site Not yet recruiting
St Leonards, Australia, 2065
Brazil
Research Site Not yet recruiting
Porto Alegre, Brazil, 90035-903
Research Site Not yet recruiting
Ribeirão Preto, Brazil, 14051-140
Research Site Not yet recruiting
São Paulo, Brazil, 045202-001
Canada, Alberta
Research Site Not yet recruiting
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Research Site Not yet recruiting
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
Research Site Not yet recruiting
Montreal, Quebec, Canada, H4A 3J1
China
Research Site Not yet recruiting
Beijing, China, 100070
Research Site Not yet recruiting
Beijing, China, 100730
Research Site Not yet recruiting
Guangzhou, China, 510060
Research Site Not yet recruiting
Shenyang, China, 110001
Germany
Research Site Withdrawn
Hamburg, Germany, 20246
Research Site Not yet recruiting
Hamburg, Germany, 20246
Research Site Not yet recruiting
Tübingen, Germany, 72076
Research Site Not yet recruiting
Würzburg, Germany, 97080
Italy
Research Site Withdrawn
Bergamo, Italy, 24127
Research Site Withdrawn
Genova, Italy, 16100
Research Site Not yet recruiting
Milano, Italy, 20133
Research Site Not yet recruiting
Napoli, Italy, 80131
Research Site Not yet recruiting
Roma, Italy, 00165
Research Site Not yet recruiting
Udine, Italy, 33100
Japan
Research Site Not yet recruiting
Minato-ku, Japan, 105-8471
Research Site Not yet recruiting
Nagoya-shi, Japan, 466-8560
Research Site Not yet recruiting
Shinjuku-ku, Japan, 160-8582
Netherlands
Research Site Withdrawn
Rotterdam, Netherlands, 3015 GD
Russian Federation
Research Site Not yet recruiting
Moscow, Russian Federation, 115522
Research Site Not yet recruiting
Moscow, Russian Federation, 125047
Research Site Recruiting
Moscow, Russian Federation, 125412
Spain
Research Site Not yet recruiting
Badalona, Spain, 08916
Research Site Not yet recruiting
Madrid, Spain, 28041
United Kingdom
Research Site Not yet recruiting
London, United Kingdom, SE1 9RT
Research Site Not yet recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
AstraZeneca
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Geraldine O'Sullivan Coyne, MD PhD National Cancer Institute (NCI)
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04924608    
Other Study ID Numbers: D134BC00001
2020-005607-39 ( EudraCT Number )
First Posted: June 14, 2021    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Neurofibromatosis Type 1
NF1
Plexiform Neurofibroma (PN)
PNs
Selumetinib
MEK inhibitor
Additional relevant MeSH terms:
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Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Neurofibroma, Plexiform
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms