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

NCT04590235 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: D1346C00011
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Neurofibromatosis 1; Neurofibroma Plexiform

Keywords

Neurofibromatosis Type 1; Plexiform Neurofibromas; Phase 1; Selumetinib; Chinese; Paediatric; Adult

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (14)

• objective response rate (ORR) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas

  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

  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

  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

  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

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

Study Arms (1)

Selumetinib

EXPERIMENTAL

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

Selumetinib DRUG

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

Selumetinib

Eligibility Criteria

• Age: 3 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Research Site

Shanghai, 200011, China

Location

Research Site

Shanghai, CN-200092, China

Location

Related Links

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

MeSH Terms

Conditions

Neurofibromatosis 1; Neurofibroma, Plexiform

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; 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; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Study Officials

• Qingfeng Li

  Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: October 19, 2020
• Study Start: December 16, 2020
• Primary Completion: August 16, 2022
• Study Completion (Estimated): August 31, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

CN (2)