Phase 2a non-commercial and non-randomized intervention study evaluating the efficacy of crizotinib in the treatment of children with severe type 2 neurofibromatosis, in particular those excluded from surgery and / or radiotherapy

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• children who: 1a. they will not be able to swallow the medicine tablet whole 1b. are or during the last 4 months have been actively treated with chemotherapy or other biological therapies, are undergoing radiotherapy or have been treated with therapeutic irradiation (regardless of the method and source of radiotherapy) in the period from 4 to 10 months before qualifying for a clinical trial 1c. remain immediately or up to 6 months after neurosurgery, in particular with unstable intracranial hypertension (regardless of the cause) 1d. participate in another therapeutic clinical trial conducted for them for any reason (excluding observational studies) 1e. do not meet the inclusion criteria, in particular due to comorbidities causing the risk of complications of crizotinib treatment: uncontrolled or moderate and severe arterial hypertension, broadly defined arrhythmias requiring treatment, severe defects and/or heart failure requiring treatment, renal and/or liver failure above mild (for liver - above Child-Pugh class C), chronic lung disease with symptoms of respiratory failure (O2 saturation <95% at rest and at room temperature) 1f. are treated for diseases of the digestive system that cause intestinal absorption disorders (short intestine, uncontrolled celiac disease, chronic malnutrition/cachexia and anorexia, chronic diseases with nausea, vomiting and diarrhea, Crohn's disease and ulcerative colitis) 1g. require treatment with substances that are inhibitors or inducers of the following enzymes of the cytochrome system: o CYP3A4 (inhibitors such as atazanavir, ritonavir, cobicistat, itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin and erythromycin, as well as grapefruit and grapefruit juice) o CYP3A4 (strong and moderate inducers such as carbamazepine, phenobarbital, phenytoin, rifampicin, St. John's wort and moderate inducers such as rifabutin, efavirenz) o CYP2B6 (e.g. bupropion, efavirenz) 1h. require concomitant use of drugs that interact pharmacologically with crizotinib listed in the SmPC o especially with CYP3A4 substrates with a low therapeutic index (midazolam, alfentanil, cisapride, cyclosporine, ergot derivatives, fentanyl, pimozide, quinidine, sirolimus and tacrolimus) o drugs metabolized mainly by UDP-glucuronyltransferases: UGT1A1 (e.g. raltegravir, irinotecan) or UGT2B7 (e.g. morphine, naloxone) o drugs that slow the heart rate, drugs that prolong the QT interval and/or antiarrhythmic drugs that may prolong the QT interval or induce torsades de pointes (e.g. class IA antiarrhythmics such as quinidine, disopyramide or class III antiarrhythmics such as amiodarone, sotalol, dofetilide, ibutilide and methadone, cisapride, moxifloxacin, neuroleptics, etc.) or bradycardia-inducing drugs (e.g. non-dihydropyridine calcium channel blockers such as verapamil and diltiazem; beta blockers, clonidine, guanfacine, digoxin , mefloquine, cholinesterase inhibitors, ilocarpine). 1i. children with unstable malignancy or rapidly progressing malignant tumors of any origin, especially CNS tumors requiring emergency treatment for intracranial hypertension 1j. the patient's parents have limited custody of the child or family during the divorce proceedings 1k. pregnant or lactating patients.