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 to < 7 Years with Neurofibromatosis Type 1 (NF1) Related Symptomatic, Inoperable Plexiform Neurofibromas (PN) (SPRINKLE) - SPRINKLE

AstraZeneca AB0 sites38 target enrollmentOctober 19, 2021

Conditionseurofibromatosis Type 1 (NF1) Related Plexiform Neurofibromas (PN)MedDRA version: 20.0Level: LLTClassification code 10029270Term: Neurofibromatosis, type 1 (von Recklinghausen's disease)System Organ Class: 100000004850 Therapeutic area: Not possible to specify

DrugsKoselugo 10mg Koselugo 25mg

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: eurofibromatosis Type 1 (NF1) Related Plexiform Neurofibromas (PN)
Sponsor: AstraZeneca AB
Enrollment: 38
Status: Active, not recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

October 19, 2021

End Date

TBD

Last Updated

4 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

AstraZeneca AB

Eligibility Criteria

Inclusion Criteria

•1\. Male and female participants aged \= 1 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 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 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\.
•5\. Participants must have a BSA \= 0\.4 and \= 1\.09 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
•Are the trial subjects under 18? yes
•Number of subjects for this age range: 38
•F.1\.2 Adults (18\-64 years) no
•F.1\.2\.1 Number of subjects for this age range

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 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 × the ULN for age with the exception of those with Gilbert syndrome (\= 3 × ULN) or AST/ALT \> 2 × 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 to \< 4 years) or \> 1\.0 mg/dL (for participants aged \= 4 years).
•8\. Have inadequate haematological function defined as: An absolute neutrophil count \< 1500/µL or Haemoglobin \< 9g/dL or Platelets \< 100,000/µL or Have had a transfusion (of red cells or other blood derived products) within the 28 days prior to study entry (date of ICF signature).
•9\. Participants with ophthalmological findings/condition as listed in the protocol.
•10\. Have any unresolved chronic toxicity with CTCAE Grade \= 2 which are associated with previous therapy for NF1\-PN (except hair changes such as alopecia or hair lightening)