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Active, not recruitingNCT04590235Updated Aug 18, 2026

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

A Phase 1 interventional study of Selumetinib in Neurofibromatosis 1 and Neurofibroma Plexiform, sponsored by AstraZeneca. Active, not recruiting at 2 sites in China. Open to participants aged 3 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-08-18.

Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
32
Allocation
Non-randomized
Ages
3 Years to 99 Years
Sex
All
01

Study summary

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).

Read the 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

02

Conditions studied

  • Neurofibromatosis 1
  • Neurofibroma Plexiform

Keywords

  • Neurofibromatosis Type 1
  • Plexiform Neurofibromas
  • Phase 1
  • Selumetinib
  • Chinese
  • Paediatric
  • Adult
03

Who can participate

Ages eligible
3 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
32 participants (actual)

Study arms

  • 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

Interventions

  • DrugSelumetinib

    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.

    Also known as: Koselugo

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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.

  2. 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

    Time frame: From the first consent patient first dose to last patient steady state PK collection. Expected duration is approximately 1 year.

  3. 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

    Time frame: From the first consent patient first dose to last patient steady state PK collection. Expected duration is approximately 1 year.

  4. 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

    Time frame: From the first consent patient first dose to last patient steady state PK collection. Expected duration is approximately 1 year.

Secondary outcomes

  1. 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

    Time frame: First patient first dose until up to 2 years after last subject dosed

  2. 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

    Time frame: First patient first dose until up to 2 years after last subject dosed

  3. 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

    Time frame: First patient first dose until up to 2 years after last subject dosed

  4. 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

    Time frame: First patient first dose until up to 2 years after last subject dosed

  5. 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

    Time frame: First patient first dose until up to 2 years after last subject dosed

  6. Measures of Physical function via Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire

    Time frame: First patient first dose until up to 2 years after last subject dosed

  7. Measures health-related quality of life (HRQoL) via PedsQL (paediatric cohort, self-and parent-reported)

    Time frame: First patient first dose until up to 2 years after last subject dosed

  8. Measures of pain via FLACC scale

    Time frame: First patient first dose until up to 2 years after last subject dosed

  9. Measures health-related quality of life (HRQoL) via EORTC QLQ-C30 (adult cohort)

    Time frame: First patient first dose until up to 2 years after last subject dosed

  10. Measures health-related quality of life (HRQoL) via PlexiQoL (adult cohort)

    Time frame: First patient first dose until up to 2 years after last subject dosed

  11. Measures of pain via Faces Pain Scale (revised)

    Time frame: First patient first dose until up to 2 years after last subject dosed

  12. Measures of pain via NRS-11

    Time frame: First patient first dose until up to 2 years after last subject dosed

  13. Measures of pain via PII

    Time frame: First patient first dose until up to 2 years after last subject dosed

  14. Measures of pain via Pain Medication Survey

    Time frame: First patient first dose until up to 2 years after last subject dosed

06

Study locations

2 sites
  • Research Site
    Shanghai, 200011, China
  • Research Site
    Shanghai, CN-200092, China
07

References and documents

Publications

  • Zhang X, Sui W, Zheng H, Chen J, Yuan X. Durable responses to long-term selumetinib in Chinese pediatric NF1 patients with inoperable plexiform neurofibromas. Front Pharmacol. 2026 Jun 18;17:1855171. doi: 10.3389/fphar.2026.1855171. eCollection 2026. PubMed 42394972 ↗

Individual participant data

Plan to share: Yes — 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.

08

Registry details

Key details

Study ID
NCT04590235
Lead sponsor
AstraZeneca
Collaborators
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Oct 19, 2020
Start date
Dec 16, 2020
Primary completion
Aug 16, 2022
Completion
Aug 31, 2026 (estimated)
Last update
Aug 18, 2026

Study contacts

Qingfeng Li
principal investigator · Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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