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.
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.
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
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).
Single group
Selumetinib
DrugSelumetinib 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.
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;
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.
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.
Assess safety and tolerability especially for selumetinib
Incidence and severity of treatment -adverse events of ocular toxicity and cardiac toxicity graded according to CTCAE v6.0
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Beijing Tiantan Hospital
Lead sponsor
AstraZeneca
Collaborator
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