A paediatric phase I/II study of intermittent dosing of the MEK-1 inhibitor selumetinib in children with neurofibromatosis type-1 and inoperable plexiform neurofibroma and/or progressive optic pathway glaiom - Intermittent Selumetinib dosing Phase I/II study Childhood NF1 tumours

Great Ormond Street Hospital0 sites38 target enrollmentJune 19, 2019

ConditionsNeurofibromatosis type 1 associated plexiform neurofibromas Neurofibromatosis type 1 associated progressive or relapsed optic pathway glioma MedDRA version: 20.0 Level: LLT Classification code 10029270 Term: Neurofibromatosis, type 1 (von Recklinghausen's disease) System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10065866 Term: Plexiform neurofibroma System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10030935 Term: Optic nerve glioma System Organ Class: 100000004864 Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Neurofibromatosis type 1 associated plexiform neurofibromas Neurofibromatosis type 1 associated progressive or relapsed optic pathway glioma
Sponsor: Great Ormond Street Hospital
Enrollment: 38
Status: Active, not recruiting
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

June 19, 2019

End Date

TBD

Last Updated

6 years ago

Study Type

Interventional clinical trial of medicinal product

Investigators

Sponsor

Great Ormond Street Hospital

Eligibility Criteria

Inclusion Criteria

•1\.Age Phase I: \=3 years and \=18 years of age at the time of study enrolment, if able to swallow whole capsules.
•Age Phase II: \=3 years and \= 18 years. BSA \= 0\.55 m2, if able to swallow whole capsules.
•2\.Diagnosis: Phase I (Dose escalation): Patients with NF1 and inoperable PNs defined as PNs that cannot be surgically completely removed without risk for substantial morbidity.(for details refer to protocol sec 2\.1\)
•Phase 2 (Dose expansion): Two cohorts are eligible for inclusion in the dose expansion cohort.
•Cohort A (approx 10 patients) Patients with NF1 and inoperable measurable PNs (as per Phase I)
•Cohort B (approx 10 patients) NF\-1 related progressive optic pathway glioma is eligible if the patient has evidence of either clinical (e.g. worsening visual function as per REiNS) or MRI based significant radiological progression and has had at least two lines of standard therapy.
•In addition, all study subjects (phase I and II) must have either positive genetic testing for NF1 from a certified laboratory or have at least one other diagnostic criterion for NF1 listed below:
•Six or more café\-au\-lait macules (\=0\.5cm in prepubertal subjects or \=1\.5 cm in post pubertal subjects)
•Freckling in axilla or groin
•Optic glioma

Exclusion Criteria

•1\.Pregnant or breast\-feeding females are excluded due to potential risks of foetal and teratogenic adverse events of an investigational agent. Pregnancy tests must be obtained prior to enrolment on this study for girls of reproductive potential. The need to commence pregnancy testing will be at the discretion of the treating physician to facilitate taking in to account factors such as precocious puberty, endocrine status and medications which can affect pubertal status. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Abstinence is an acceptable method of birth control.
•2\.Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.
•3\.Recent major surgery within a minimum of 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access.
•4\.Phase I: Patients who anticipate the need for surgical intervention within the first three cycles (3 months), as surgical intervention during the period of DLT evaluation may affect analysis of adherence and/or make the subject in\-evaluable.
•Phase II: Patients who anticipate the need for surgical intervention of the target PN within the first eight cycles (8 months), as surgical intervention during the period may affect analysis of response and may make the subject in\-evaluable.
•5\.An investigational agent within the past 28 days.
•6\.Any unresolved chronic toxicity with toxicity \= CTCAE Grade 2 from previous anti\-cancer therapy, except for alopecia.
•7\.Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumour, immunotherapy, or biological therapy.
•8\.Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
•9\.Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.