Selumetinib in Chinese Paediatric With Post-operative NF1-PNs, PhaseⅡ, Double-Blinded, Placebo-Controlled Study — PROTECT  

Neurofibromatosis Type 1 Clinical Trial

Official title: The Efficacy of Selumetinib in Chinese Paediatric Participants With Post-operative Neurofibromatosis Type 1 (NF1)-Associated PNs: A PhaseⅡ, Multicenter, Randomised, Double-Blinded, Placebo-Controlled Study

Status Withdrawn

Clinical Trial Summary

This is a phase II, multicenter, randomised, parallel, double-blind, placebo-controlled study assessing the efficacy and safety of the MEKi selumetinib compared with placebo in Chinese paediatric participants with post-operative NF1-associated PNs.

Clinical Trial Description

Participant Population:

The target population of interest in this study is Chinese paediatric participants with post-operative NF1-associated PNs who have received sub-total or partial resection of the targeted PN lesion (residue should be > 20% of pre-operative tumour volume, and measurable, defined as a lesion of ≥3 cm measured in one dimension on ≥3 imaging slices and have a reasonably well-defined contour), at least 4 weeks and up to 3 months after surgery.

Number of Participants:

Approximately 42 Chinese paediatric participants with post-operative NF1-associated PN will be randomised in a 2:1 ratio to receive selumetinib (28 participants) or placebo (14 participants).

Treatment Groups and Duration:

Following the screening period (Day -28 to Day -1), enrolled participants will be randomised in a 2:1 ratio to one of the treatment groups. Randomisation will be stratified by age (<12 versus ≥12 years old).

Participants will orally receive selumetinib or placebo twice daily (BID) (approximately every 12 hours) at a dose of 25 mg per square meter of body surface area (BSA) on a continuous dosing schedule (28-day per cycle with no rest periods between cycles) for a maximum of 36 cycles. Participants should be instructed to take the dose of selumetinib or placebo on an empty stomach (no food or drink other than water for 2 hours before and 1 hour after dosing) with water only. The capsules cannot be crushed and must be swallowed whole.

Dosing will be performed based on BSA calculated by the equation below, and doses will be rounded to the nearest 5 to 10 mg using a dosing nomogram. BSA should be calculated at screening and every tumour assessment visit. The dose of investigational medicinal product (IMP) will be capped at 50 mg when BSA is ≥1.9 m2.

All participants will be evaluated for safety and efficacy at a regular basis, as defined in Table 1. The safety follow-up visit will be conducted at Day 28 after the end of treatment (EOT) or treatment discontinuation.

Tumour assessments, measured by 3D volumetric magnetic resonance imaging will be determined by investigators according to REiNS criteria. Participants in the placebo group can be transferred to the selumetinib group within the study, when REiNS-defined progression of disease (PD) was detected in a participant. During the intervention period, participants may continue to receive selumetinib beyond REiNS-defined PD as long as they are continuing to show clinical benefit, as judged by the investigators and Sponsor.

Participants should continue on treatment until:

Unacceptable safety & tolerability event; Participants withdraw from the study; Completing 36 cycles of treatment or 24 cycles after last participant in (whichever comes first). ;

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type 1
• Plexiform Neurofibromas
• Post-operative

• NCT number: NCT05825365
• Study type: Interventional
• Source: AstraZeneca
• Status: Withdrawn
• Phase: Phase 2
• Start date: August 31, 2023
• Completion date: June 30, 2026