Brief Title
A Study of Selumetinib in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN)
Official Title
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)
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)
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Adverse events
Secondary Outcome
objective response rate (ORR) of selumetinib in Chinese paediatric and adult subjects with Neurofibromatosis Type 1 and inoperable Plexiform Neurofibromas
Condition
Neurofibromatosis 1
Intervention
Selumetinib
Study Arms / Comparison Groups
Selumetinib
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
32
Start Date
December 16, 2020
Completion Date
September 30, 2026
Primary Completion Date
October 31, 2023
Eligibility Criteria
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.
Gender
All
Ages
3 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
Qingfeng Li, 1-877-240-9479, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04590235
Organization ID
D1346C00011
Responsible Party
Sponsor
Study Sponsor
AstraZeneca
Collaborators
Merck Sharp & Dohme Corp.
Study Sponsor
Qingfeng Li, Principal Investigator, Shanghai Ninth People's Hospital affiliated to Shanghai JiaoTong University
Verification Date
September 2021