Selumetinib for NF2-Related Schwannomatosis

NCT07707947 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HX-A-2026034
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of the MEK1/2 inhibitor selumetinib in treating patients with neurofibromatosis type 2-related schwannomatosis (NF2-SWN), including both adults and children with inoperable or progressive tumors.

Conditions

Neurofibromatosis Type 2; NF2; NF2-related Schwannomatosis; Meningioma; Ependymoma; Vestibular Schwannoma

Keywords

NF2-SWN; Selumetinib

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR)in NF2-related vestibular schwannoma assessed according to the REiNS criteria

  Partial response is defined as the sum volume of VS decrease ≥20% compared to baseline, confirmed by a consecutive scan after 1 to 3 treatment cycles after the first response. Complete response is defined as disappearance of VS, confirmed by a consecutive scan after 1 to 3 treatment cycles after the first response;

  12 months

• Hearing Response Rate Based on Word Recognition Score (WRS) in Target Vestibular Schwannoma

  Percentage of participants with WRS improvement exceeding the 95% critical difference from baseline in the ear associated with the target vestibular schwannoma.

  12 months

• Pure Tone Average (PTA) Response Rate in Target Vestibular Schwannoma

  Percentage of participants with a PTA decrease of at least 10 dB from baseline in the ear associated with the target vestibular schwannoma.

  12 months

Secondary Outcomes (1)

• Assess safety and tolerability especially for selumetinib

  From the first dose of study drug (Day 0) through 30 ± 3 days after the last dose administration.

Study Arms (1)

Selumetinib

EXPERIMENTAL

Selumetinib will be administered at a dose of 25 mg/m²orally twice daily (BID),with a maximum single dose of 50 mg per administration.Doses will be calculated based on body surface area (BSA)and rounded to the nearest 5 mg increment.

Drug: Selumetinib

Interventions

Selumetinib DRUG

Selumetinib will be administered at a dose of 25 mg/m²orally twice daily (BID),with a maximum single dose of 50 mg per administration.Doses will be calculated based on body surface area (BSA)and rounded to the nearest 5 mg increment.

Also known as: KOSELUGO

Selumetinib

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a pathogenic variant in the NF2 gene (either in the germline or in two NF2-related tumors)OR a confirmed diagnosis of NF2 by fulfilling National Institute of Health (NIH)criteria or Manchester criteria:
• The genetic test report should be issued by companies or hospitals with corresponding qualifications.
• The NIH criteria includes presence of:
• Bilateral vestibular schwannomas, OR
• First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity.
• The Manchester criteria includes presence of:
• Bilateral vestibular schwannomas, OR
• First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
• Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity,OR
• Multiple meningiomas (two or more)AND unilateral vestibular schwannoma OR
• any two of: schwannoma, glioma, neurofibroma, cataract.
• Subjects must have ≥1 measurable target vestibular schwannoma meeting all of the following conditions:
• Measurable on MRI with a minimum diameter ≥3 mm;
• Evidence of radiographic progression within the past 36 months according to REiNS criteria, OR documented clinical progression attributable to the target tumor (e.g., hearing decline, cranial nerve dysfunction).
• Subjects whose Word Recognition Score (WRS)ranging from 50%to 88%at the side of target vestibular schwannoma.

You may not qualify if:

• Concurrent involvement in study conduct:the subject is an employee of the Sponsor, Investigator, or study site who is directly involved in the planning, conduct, or management of this clinical study.
• Participation in another interventional clinical trial with an investigational medicinal product, or receipt of an investigational agent within 28 days (or 5 half-lives if known and longer)prior to first dose.
• Prior anti-cancer systemic therapies or prior radiotherapy that, in the investigator's judgment, would confound safety or efficacy assessment, unless completed ≥28 days prior to first dose (longer washout required for agents with prolonged biologic effect as specified in protocol appendix). Subjects who received prior local therapy (surgery or localized radiotherapy)are eligible if recovery is complete and target lesion remains measurable.
• Evidence or high suspicion of malignant peripheral nerve sheath tumor (MPNST)or other active malignancy requiring systemic therapy (past malignancy is allowed only if disease-free for ≥2 years, except for adequately treated basal cell carcinoma or in situ carcinoma).
• Significant cardiac disease or ECG abnormalities:
• Resting QTcF \>470 ms (adults)\[\>450 ms for pediatric thresholds as specified in protocol appendix\], or clinically significant baseline prolongation per investigator/medical monitor.
• Clinically significant arrhythmia (symptomatic ventricular tachycardia, sustained ventricular tachycardia, uncontrolled atrial fibrillation). Subjects with well controlled atrial fibrillation may be considered after Medical Monitor review.
• Acute coronary syndrome within 6 months, unstable angina, symptomatic congestive heart failure NYHA class II-IV, or LVEF below institutional lower limit of normal (LLN)or \<50%.
• Uncontrolled hypertension:systolic ≥140 mmHg or diastolic ≥90 mmHg despite optimal therapy (adult criteria);for pediatric subjects use age/height/gender percentiles per protocol appendix.
• Ophthalmologic conditions:current or prior history of MEK-associated retinopathy / central serous retinopathy /retinal pigment epithelial detachment /retinal vein occlusion, or any active ocular condition judged by the investigator/ophthalmologist to increase the risk of serious ocular adverse events (e.g., uncontrolled glaucoma with elevated IOP and meaningful vision at risk). Subjects with stable, chronic ophthalmic findings that are not expected to worsen with MEK inhibition may be eligible after ophthalmology clearance.
• Known hypersensitivity to selumetinib or any excipients.
• Active, uncontrolled infection including:
• Positive HIV test (known HIV infection with uncontrolled disease or on unstable antiretroviral therapy that interacts with study drug)-no evidence AIDS and no contraindicating ART may be considered after Medical Monitor review.
• Active hepatitis B or C infection (HBsAg positive or HCV RNA positive). Subjects with resolved HBV (HBsAg negative, anti-HBc positive)may be eligible per local hepatology guidance and prophylaxis plan.
• Concomitant medications that:

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• AstraZeneca: collaborator

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

MeSH Terms

Conditions

Neurofibromatosis 2; Meningioma; Ependymoma; Neuroma, Acoustic

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial; Peripheral Nervous System Neoplasms

Central Study Contacts

Pinan Liu, PhD

CONTACT

010-59976611; pinanliu@ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Selumetinib will be administered at a dose of 25 mg/m²orally twice daily (BID),with a maximum single dose of 50 mg per administration.Doses will be calculated based on body surface area (BSA)and rounded to the nearest 5 mg increment.

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 16, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)