A Phase I/II, Single-Arm, Open label Study to Evaluate the Pharmacokinetics, Safety/Tolerability and Efficacy of the Selumetinib Granule Formulation in Children Aged 1 or more to < 7 Years with Neurofibromatosis Type 1 (NF1) Related Symptomatic, Inoperable Plexiform Neurofibromas (PN) (SPRINKLE) - SPRINKLE

Kobayashi Hiroshi0 sites6 target enrollmentNovember 25, 2022

Conditionseurofibromatosis 1, Plexiform Neurofibroma (PN)

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: eurofibromatosis 1, Plexiform Neurofibroma (PN)
Sponsor: Kobayashi Hiroshi
Enrollment: 6
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

November 25, 2022

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional

Sex

All

Investigators

Sponsor

Kobayashi Hiroshi

Eligibility Criteria

Inclusion Criteria

•1\.Male and female participants aged 1 or more to \< 7 years of age at the time their legally authorised representative (parent or guardian) signs the informed consent.
•2\.All study participants must be diagnosed with NF1 with symptomatic inoperable PN as defined in protocol.
•3\.Participants must have at least one measurable PN, defined as a PN of at least 3 cm measured in one dimension, which can be seen on at least 3 imaging slices and have a reasonably well\-defined contour. Participants who have undergone surgery for resection of a PN are eligible provided the PN was incompletely resected and is measurable. The target PN will be defined as the clinically most relevant PN, which is symptomatic, inoperable and measurable by volumetric MRI analysis.
•4\.Performance status: Participants must have a Lansky performance of 70 or more except in participants who are wheelchair bound or have limited mobility secondary to a need for mechanical breathing support (such as an airway PN requiring tracheostomy or continuous positive airway pressure) who must have a Lansky performance of 40 or more.
•5\.Participants must have a BSA 0\.4 or more and 1\.09 or less m2 at study entry (date of ICF signature).
•6\.Mandatory provision of consent for the study signed and dated by a participant's legally authorised representative (parent or guardian) along with the paediatric assent form, if applicable.

Exclusion Criteria

•1\.Participants with confirmed or suspected malignant glioma or MPNST. Participants with low grade glioma (including optic glioma) not requiring systemic therapy are permitted.
•2\.History of malignancy except for malignancy treatment with curative intent with no known active disease 2 or more years before the first dose of study intervention and of low potential risk of recurrence.
•3\.Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of selumetinib.
•4\.A life\-threatening illness, medical condition, organ system dysfunction or laboratory finding which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of selumetinib, or put the study outcomes at undue risk.
•5\.Participants with clinically significant cardiovascular disease as defined in the protocol.
•6\.Liver function tests: Bilirubin \> 1\.5 x the ULN for age with the exception of those with Gilbert syndrome (3 or more x ULN) or AST/ALT \> 2 x ULN.
•7\.Renal Function: Creatinine clearance or radioisotope glomerular filtration rate \< 60 mL/min/1\.73 m2 or Serum creatinine \> 0\.8 mg/dL (for participants aged 1 or more to \< 4 years) or \> 1\.0 mg/dL (for participants aged 4 or more years).
•8\.Participants with ophthalmological findings/condition as listed in the protocol.
•9\.Have any unresolved chronic toxicity with CTCAE Grade 2 or more which are associated with previous therapy for NF1\-PN (except hair changes such as alopecia or hair lightening)
•10\.Participants who have previously been treated with a MEKi (including selumetinib) and have had disease progression, or due to toxicity have either discontinued treatment and/or required a dose reduction.