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OpenTrials
Active, Not Recruiting

NCT Number: NCT04924608

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

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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Neurofibromatosis 1 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Neoplasms Neoplasms by Histologic Type Neoplasms, Nerve Tissue Neoplastic Syndromes, Hereditary Nerve Sheath Neoplasms Nervous System Diseases Nervous System Neoplasms Neurocutaneous Syndromes Neurodegenerative Diseases Neurofibroma Neurofibroma, Plexiform Neurofibromatoses Neuromuscular Diseases Peripheral Nervous System Diseases Peripheral Nervous System Neoplasms Plexiform Neurofibroma (PN)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Melbourne, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Selumetinib

Drug

Selumetinib oral capsules (10 mg and 25 mg)

Other names: AZD6244

Placebo

Other

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

Primary outcomes

  1. Confirmed Partial and Complete Response Rate (ORR) by End of Cycle 16 Using Volumetric MRI Analysis as Determined by ICR (Per REiNS Criteria) in Participants With NF1 Who Have Symptomatic, Inoperable PN.

    Time frame: From first dose up until progression (if it occurs prior to the end of Cycle 16), or the last evaluable assessment up to and including the end of Cycle 16, excluding MRI during prolonged study intervention interruption (defined as interruption >= 28 days)

    Objective response rate is defined as the proportion of participants who have a confirmed CR (defined as disappearance of the target PN, confirmed by a consecutive scan within 3 to 6 months after the first response) or confirmed PR (defined as a target PN volume decrease ≥ 20%, compared to baseline, confirmed by a consecutive scan within 3 to 6 months after the first response) by end of Cycle 16 as determined by ICR per REiNS criteria.

    Increase in the volume of the target PN by 20% or more compared to baseline or the time of best response after documenting a PR is considered as PD.

Secondary outcomes

  1. (First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Primary Analysis

    Time frame: Baseline and end of cycle 12 of study intervention

    The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo in participants with a PAINS-pNF chronic target PN pain score of ≥ 3 at baseline is presented.

  2. (First Key Secondary) The Difference of the Means in the Change From Baseline in PAINS-pNF Chronic Target PN Pain Intensity Score at Cycle 12 Between Selumetinib and Placebo, Supplemental Analysis

    Time frame: Baseline and end of cycle 12 of study intervention

    The PAINS-pNF (Pain Intensity Scale for Plexiform Neurofibroma) chronic target PN pain intensity measures the participants' experience of chronic PN-related pain intensity with score from 0 (no chronic tumor pain) to 10 (worst chronic tumor pain). Baseline PAINS-pNF chronic target PN pain score is defined as the average of the available daily PAINS-pNF chronic target PN pain scores in the screening perio, while for Cycle 12, it is defined as the average of the available daily scores for the 28-days cycle up to and including the last day assessment of cycle 12. The difference of the means in the change from baseline at Cycle 12 between selumetinib and placebo participants is presented.

  3. (Second Key Secondary Endpoint) The Difference of the Means in the Change From Baseline in PlexiQoL Total Score at Cycle 12

    Time frame: Baseline and end of Cycle 12 of study intervention

    PlexiQoL (Plexiform Neurofibroma Quality of Life scale) is a patient-derived QoL measure specific to adults with NF1-associated PNs. It assesses the impact of PNs on patients' ability to fulfil their human needs. The measure consists of 18 dichotomous items with 0 =Not True and 1 = True. PlexiQoL total scores were calculated by the sum of all items to a maximum of 18, with lower scores indicating better quality of life. The change from baseline to the end of each cycle in PlexiQoL total score was derived as the PlexiQoL total score at the cycle 12 minus baseline PlexiQoL total score and presented.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study 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)

Acronym: KOMET

Important dates

Study start
2021
Primary completion
2024
Study completion
2029
First posted
Jun 14, 2021
Registry last updated
Mar 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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