Intermittent Selumetinib dosing Phase I/II study Childhood NF1 tumours
Research type
Research Study
Full title
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
IRAS ID
234754
Contact name
Darren Hargrave
Contact email
Sponsor organisation
Great Ormond Street Hospital
Eudract number
2017-002635-41
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 0 months, 25 days
Research summary
The growth of plexiform neurofibromas (PN) and low grade gliomas (LGG), including optic pathway gliomas (OPG), in patients with Neurofibromatosis Type 1 (NF1) is thought to be due to MEK activation. Selumetinib is a MEK inhibitor.
2 studies in the USA have demonstrated promising preliminary activity of Selumetinib in children with NF1. One study tested selumetinib in children with NF1 and inoperable plexiform neurofibromas, the other tested selumetinib in children with NF1 related LGG. In both studies selumetinib was given twice a day, every day and the maximum tolerated dose (MTD) in both studies was 25mg/m2/dose. This dose was less than the adult MTD of 40mg/m2/day. There is interest in exploring an alternative intermittent dosing schedule in children to ascertain if a higher MTD can be achieved compared to the current continuous schedule and whether the safety profile and efficacy is the same or improved with a 2 day drug holiday each week.
In this study, Selumetinib will be given twice daily, 5 days out of 7 to NF-1 children aged 3 to ≤18 years. Phase 1, (dose escalation) is designed to establish the MTD and recommended phase 2 dose. It will be open to NF-1 children with inoperable PN. The Phase 2 part of the study will be open to 2 groups of patients.
1: NF-1 related relapsing/progressive OPG,
2: NF1 related inoperable progressive PN.Phase 2 of the study will only commence when the MTD is established. The purpose of Phase 2 is to determine the effectiveness of the 5 out of 7 day intermittent dosing schedule of Selumetinib, using response rates (and duration of response), appropriate MRI criteria and functional assessments.
This study is sponsored by Great Ormond Street Hospital and carried out in collaboration with Astrazeneca, who are providing drug support and funding for the study.
REC name
London - Hampstead Research Ethics Committee
REC reference
18/LO/0704
Date of REC Opinion
19 Jun 2018
REC opinion
Further Information Favourable Opinion