A Study of Selumetinib in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN)

A Phase 1 Open Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Selumetinib, a Selective Mitogen Activated Protein Kinase Kinase (MEK) 1 Inhibitor, in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN)

A Phase 1 Open Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Selumetinib, a Selective Mitogen Activated Protein Kinase Kinase (MEK) 1 Inhibitor, in Chinese Paediatric and Adult Subjects with Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN).

Study Overview

• Status: Active, not recruiting
• Conditions: Neurofibromatosis 1; Neurofibroma Plexiform
• Intervention / Treatment: Drug: Selumetinib

Detailed Description

Paediatric and adult patients with Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN) will be evaluated in the screening visit to confirm eligibility. Approximately 16 paediatric and 16 adult qualified patients will receive oral selumetinib 25 mg/m^2 twice a day (approximately every 12 hours) continuously until disease progression or unacceptable drug-related toxicity, whichever occurs first. Once a patient has discontinued the study treatment then the patient will be followed for specified period for safety assessment

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200011
    • Research Site
  • Shanghai, China, CN-200092
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Paediatric cohort: Chinese subjects ≥3 years and <18 years of age
• Adult cohort: Chinese subjects ≥18 years of age at the time of study enrollment
• Subjects must be diagnosed with (i) NF1 as per NIH Consensus Development Conference Statement and（ii) PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches. (iii) inoperable PN
• Subjects must have at least one measurable typical or nodular PN
• Absolute neutrophil count ≥1.5×10^9/L, haemoglobin ≥9g/dL, and platelet count ≥100×10^9/L. Subject must be without growth factor support and platelet transfusion support 7 days before the screening assessment.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2×upper limit of normal (ULN), total bilirubin ≤1.5×ULN except in the case of subjects with documented Gilbert's disease (≤2.5×ULN).

Exclusion Criteria:

• Evidence of malignant peripheral nerve sheath tumour.
• Clinically significant cardiovascular disease
• Prior malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to <2 years) or other cancer requiring treatment with chemotherapy or radiation therapy.
• Subjects with the following ophthalmological findings/conditions:

Current or past history of retinal pigment epithelial detachment/central serous retinopathy or retinal vein occlusion; Intraocular pressure >21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP); Subjects with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study physician; Any other significant abnormality on ophthalmic examination that would make the subject unsuitable for enrolment into the study, as assessed by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Selumetinib; All eligible subjects will first receive a single oral dose of selumetinib 25 mg/m^2. Then, selumetinib 25 mg/m^2 oral twice daily will be administered continuously until disease progression or unacceptable drug-related toxicity, whichever occurs first.

Drug: Selumetinib; All eligible subjects will first receive a single oral dose of selumetinib 25 mg/m^2. After a washout period of 2 days, oral selumetinib 25 mg/m^2 twice daily will be administered continuously. Subjects will continue to receive selumetinib until disease progression or unacceptable drug-related toxicity, whichever occurs first. 10 mg and 25 mg capsules strengths available.; Other Names: Koselugo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Occurrence/frequency.; Relationship to IP as assessed by investigator.; Common Terminology Criteria for Adverse Events (CTCAE) grade.; Seriousness.; Death.; Adverse events leading to discontinuation of IP.; Adverse events of special interest.	For paediatric cohort: from signing the informed consent form until up to 3 years after last subject dosed; For adult cohort: from signing the informed consent form until up to 2 years+30 days after last subject dosed.
Area under the concentration-time curve from zero to the last measurable concentration (AUC0-t) of selumetinib and its metabolite (N-desmethyl selumetinib) in Chinese paediatric and adult subjects with NF 1 and inoperable Plexiform Neurofibromas	AUC0-t after single dose and multiple doses administration	From the first consent patient first dose to last patient steady state PK collection. Expected duration is approximately 1 year.
Maximum plasma concentration (Cmax) of selumetinib and its metabolite (N-desmethyl selumetinib) in Chinese paediatric and adult subjects with NF 1 and inoperable Plexiform Neurofibromas	Cmax after single dose and multiple doses administration	From the first consent patient first dose to last patient steady state PK collection. Expected duration is approximately 1 year.
Terminal half-life (t1/2) of selumetinib and its metabolite (N-desmethyl selumetinib) in Chinese paediatric and adult subjects with NF 1 and inoperable Plexiform Neurofibromas	t1/2 after single dose and multiple doses administration	From the first consent patient first dose to last patient steady state PK collection. Expected duration is approximately 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas	measured by 3D volumetric magnetic resonance imaging (MRI) of the target and nontarget PN	First patient first dose until up to 2 years after last subject dosed
duration of response (DoR) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas	measured by 3D volumetric magnetic resonance imaging (MRI) of the target and nontarget PN	First patient first dose until up to 2 years after last subject dosed
progression-free survival (PFS) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas	measured by 3D volumetric magnetic resonance imaging (MRI) of the target and nontarget PN	First patient first dose until up to 2 years after last subject dosed
time to progression (TTP) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas	measured by 3D volumetric magnetic resonance imaging (MRI) of the target and nontarget PN	First patient first dose until up to 2 years after last subject dosed
time to response (TTR) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas	measured by 3D volumetric magnetic resonance imaging (MRI) of the target and nontarget PN	First patient first dose until up to 2 years after last subject dosed
Measures of Physical function via Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire		First patient first dose until up to 2 years after last subject dosed
Measures health-related quality of life (HRQoL) via PedsQL (paediatric cohort, self-and parent-reported)		First patient first dose until up to 2 years after last subject dosed
Measures of pain via FLACC scale		First patient first dose until up to 2 years after last subject dosed
Measures health-related quality of life (HRQoL) via EORTC QLQ-C30 (adult cohort)		First patient first dose until up to 2 years after last subject dosed
Measures health-related quality of life (HRQoL) via PlexiQoL (adult cohort)		First patient first dose until up to 2 years after last subject dosed
Measures of pain via Faces Pain Scale (revised)		First patient first dose until up to 2 years after last subject dosed
Measures of pain via NRS-11		First patient first dose until up to 2 years after last subject dosed
Measures of pain via PII		First patient first dose until up to 2 years after last subject dosed
Measures of pain via Pain Medication Survey		First patient first dose until up to 2 years after last subject dosed

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Qingfeng Li, Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University

Publications and helpful links

Helpful Links

• Clinical Study Protocol Redacted
• SAP Redacted
• CSR Synopsis Redacted
• Study Results

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): August 16, 2022
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chinese; Phase 1; Adult; Paediatric; Neurofibromatosis Type 1; Selumetinib; Plexiform Neurofibromas
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibroma; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma, Plexiform; AZD 6244
• Other Study ID Numbers: D1346C00011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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 rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes