Could a cancer drug shrink brain tumors and save hearing in a rare nerve disorder?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. 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. 2. 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. 3. The target tumor must be considered not amenable to surgery due to: * High surgical risk (e.g., risk of neurological deficit), OR * Patient refusal of surgery after adequate medical counseling. 4. Male or female subjects aged ≥3 years at the time of informed consent. 5. Adequate functional status Subjects aged ≥16 years: * Karnofsky Performance Status ≥70,OR * ECOG Performance Status 0-1 Subjects aged \<16 years: * Lansky Performance Status ≥70 * Adequate organ and bone marrow function 6. Laboratory values obtained within 28 days prior to enrollment must meet the following: 1. Hematologic function * Hemoglobin ≥9.0 g/dL * Absolute neutrophil count (ANC)≥1.5 ×10⁹/L * Platelet count ≥100 ×10⁹/L 2. Hepatic function * AST and ALT ≤2.5 ×ULN (≤2.0 ×ULN for pediatric subjects) * Total bilirubin ≤ 1.5 ×ULN (≤3 ×ULN in subjects with documented Gilbert's syndrome) 3. Renal function * Serum creatinine ≤1.5 ×ULN, OR * Creatinine clearance ≥60 mL/min/1 .73 m²(age-and BSA-adjusted) 4. Cardiac function * Left ventricular ejection fraction (LVEF)≥50%by echocardiography * No clinically significant uncontrolled cardiac disease 5. Pulmonary function • Peripheral oxygen saturation ≥92%on room air 7. Reproductive and contraception requirements 1. Females of childbearing potential * Negative serum or urine pregnancy test prior to enrollment * Must be postmenopausal ≥12 months, surgically sterile, or using a highly effective method of contraception throughout the study and for 3 months after the last dose * Acceptable methods include: * Hormonal contraception * Intrauterine device (IUD) * Long-acting reversible contraception * Tubal ligation * Oral contraception alone must be combined with a barrier method 2. Males • Must be surgically sterile or agree to use barrier contraception with permicide during treatment and for 3 months after the last dose. 8. Subjects must be able to swallow selumetinib capsules intact. 9. Written informed consent must be obtained: * From the subject if capable of providing consent; * From a legally acceptable representative for minors or subjects lacking full decision-making capacity. Exclusion Criteria: 1. 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. 2. 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. 3. 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. 4. 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). 5. 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%. 6. 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. 7. Severe hepatic or renal impairment -e.g.,AST/ALT \>5 ×ULN (or per protocol specified threshold for severe impairment), total bilirubin \>3 ×ULN (unless Gilbert's syndrome).(See inclusion for minimum acceptable labs;exclude those with more severe dysfunction.) 8. 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. 9. Known hypersensitivity to selumetinib or any excipients. 10. 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. 11. Concomitant medications that: * Are known to prolong QT interval and cannot be safely discontinued;OR * Are strong CYP3A4 or CYP2C19 inducers/inhibitors that cannot be stopped and would significantly alter selumetinib exposure (refer to protocol drug-interaction appendix for permitted/forbidden lists). 12. Gastrointestinal conditions that preclude reliable oral absorption (e.g., severe malabsorption, short bowel syndrome, recent (within 6 months)major intestinal resection)or inability to swallow intact capsules. 13. Conditions requiring urgent neurosurgical intervention (e.g., symptomatic hydrocephalus requiring immediate shunting, life-threatening brainstem compression)-subjects requiring emergent neurosurgery are not eligible until stabilized and reevaluated. 14. Prior organ transplantation (allogeneic)or ongoing immunosuppression that would confound safety assessment. 15. Concomitant vitamin E†or other agents judged to have potential interaction with the study drug if they cannot be discontinued per protocol (e.g., vitamin E to be stopped ≥7 days before first dose if required by protocol). 16. Pregnancy or breastfeeding at screening (positive pregnancy test). Female subjects of childbearing potential who are unwilling/unable to use acceptable contraception during the study and for the duration specified in the contraceptive guidance (see protocol)are excluded. 17. Any other clinically significant medical, psychiatric, or social condition that, in the opinion of the investigator or Medical Monitor, would compromise subject safety or protocol compliance (including inability to undergo MRI, when MRI is required for tumor assessment).