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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04924608
Collaborator
Merck Sharp & Dohme LLC (Industry)
146
41
2
42.1
3.6
0.1

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Nov 19, 2021
Anticipated Primary Completion Date :
Oct 24, 2024
Anticipated Study Completion Date :
May 22, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

Selumetinib

Drug: Selumetinib
Selumetinib oral capsules (10 mg and 25 mg)
Other Names:
  • AZD6244
  • Placebo Comparator: Arm B

    Placebo

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

    Outcome Measures

    Primary Outcome Measures

    1. Confirmed Objective Response Rate (ORR) for Arm A versus Arm B [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [Approximately 3 years]

      Selumetinib and N-desmethyl selumetinib plasma concentrations assessment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Gainesville Florida United States 32610
    2 Research Site Rockville Maryland United States 20852
    3 Research Site Saint Louis Missouri United States 63156
    4 Research Site Commack New York United States 11725
    5 Research Site Richmond Virginia United States 23219
    6 Research Site Melbourne Australia 3000
    7 Research Site St Leonards Australia 2065
    8 Research Site Porto Alegre Brazil 90035-903
    9 Research Site Ribeirão Preto Brazil 14051-140
    10 Research Site São Paulo Brazil 045202-001
    11 Research Site Calgary Alberta Canada T2N 4N2
    12 Research Site Toronto Ontario Canada M5G 2C4
    13 Research Site Montreal Quebec Canada H4A 3J1
    14 Research Site Beijing China 100070
    15 Research Site Beijing China 100730
    16 Research Site Guangzhou China 510060
    17 Research Site Shenyang China 110001
    18 Research Site Creteil France 94010
    19 Research Site Lyon France 69008
    20 Research Site Nantes cedex 1 France 44093
    21 Research Site Toulouse Cedex 09 France 31059
    22 Research Site Hamburg Germany 20246
    23 Research Site Hamburg Germany 20246
    24 Research Site Tübingen Germany 72076
    25 Research Site Würzburg Germany 97080
    26 Research Site Milano Italy 20133
    27 Research Site Napoli Italy 80131
    28 Research Site Roma Italy 00165
    29 Research Site Trieste Italy 34100
    30 Research Site Minato-ku Japan 105-8471
    31 Research Site Nagoya-shi Japan 466-8560
    32 Research Site Shinjuku-ku Japan 160-8582
    33 Research Site Bydgoszcz Poland 85-094
    34 Research Site Gdańsk Poland 80-952
    35 Research Site Moscow Russian Federation 115522
    36 Research Site Moscow Russian Federation 125047
    37 Research Site Moscow Russian Federation 125412
    38 Research Site Badalona Spain 08916
    39 Research Site Madrid Spain 28041
    40 Research Site London United Kingdom SE1 9RT
    41 Research Site Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • AstraZeneca
    • Merck Sharp & Dohme LLC

    Investigators

    • Principal Investigator: Geraldine O'Sullivan Coyne, MD PhD, National Cancer Institute (NCI)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04924608
    Other Study ID Numbers:
    • D134BC00001
    • 2020-005607-39
    First Posted:
    Jun 14, 2021
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 23, 2022