CRIZOTINIB for Neurofibromatosis type 2

Inclusion criteria

• {"criterion_text":"- children meeting the clinical criteria for the diagnosis of NF-2 (NIH/1991 criteria after the Manchester revision of 1992) with the presence of multifocal neoplastic lesions in the central and/or peripheral nervous system\n- children from 4 years of age to 15 years of age who are able to swallow the drug tablet whole\n- children with: 3a. volumetric magnetic resonance (MR) studies showed steady progression (>10% of tumor weight over 4 to 12 months) of at least one measurable multifocal or polycyclic tumor lesion to objectively assess imaging response using system assessment criteria RECIST 1.1 (response evaluation criteria in solid crowds) 3b. there were no contraindications to the use of crizotinib specified in the Summary of Product Characteristics 3c. the function of the hematopoietic system allows treatment in accordance with the current Summary of Product Characteristics (in particular, the absolute neutrophil count is >1,500/µl and platelets >100,000/µl) 3d. renal function allows treatment (creatinine level not exceeding 1 mg/ml in children up to 13 years of age and 1.5 mg/ml in older children, including boys) 3e. bilirubin is less than 1.5 times the upper limit of normal and transaminases and alkaline phosphatase are less than 2.5 times the upper limit of normal;\n- children about: 4a. expected survival of more than one year and Lansky/Karnofsky Pediatric Performance ≥ 60 4b. stabilized neurological status for at least a year, without complications of previous radiotherapy or chemotherapy (or biological therapies) found on the day of eligibility for the study,\n- children with excluded comorbidities causing the risk of complications of crizotinib treatment (see exclusion criteria)\n- children whose parents: 6a. will be able to take care of them, will be able to conduct therapy in accordance with the requirements of the treatment protocol and sign an informed consent for treatment, and have full parental rights 6b. will follow the dietary recommendations and the rules of drug administration, in particular they will avoid the use of grapefruit or grapefruit juice and preparations containing St. John's wort and other herbal preparations or marijuana derivatives (CBD oils) and dietary supplements not recommended by the researcher (unconventional therapies) 6c. each time in a situation necessitating the administration of any other drug, they will consult with the researchers the possibility of its use, knowing the possible drug interactions presented in a separate table attached to the parental copy of the written consent for treatment\n- the protocol assumes the exclusion of concomitant use of chemotherapy and other molecularly targeted drugs"}

Exclusion criteria

• {"criterion_text":"- 1a. they will not be able to swallow the medicine tablet whole\n- 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\n- 1c. remain immediately or up to 6 months after neurosurgery, in particular with unstable intracranial hypertension (regardless of the cause)\n- 1d. participate in another therapeutic clinical trial conducted for them for any reason (excluding observational studies)\n- 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)\n- 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)\n- 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)\n- 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).\n- 1i. children with unstable malignancy or rapidly progressing malignant tumors of any origin, especially CNS tumors requiring emergency treatment for intracranial hypertension\n- 1j. the patient's parents have limited custody of the child or family during the divorce proceedings\n- 1k. pregnant or lactating patients."}

Primary endpoints

• {"endpoint_text":"- Stabilization or (desirable) regression of the primary tumor","definition_or_measurement_approach":"Radiological assessment of the change in the size of the selected target tumor (radiological assessment to assess effect of crizotinib in children with NF-2); imaging response assessed using RECIST 1.1 as referenced in inclusion criteria."}

Secondary endpoints

• {"endpoint_text":"- Stabilization or (desirable) regression of the patient's primary tumor and other tumors for at least 6 months after the end of treatment","definition_or_measurement_approach":"Radiographic evaluation of persistence of crizotinib effect on the target tumor in children with NF-2 6 months after the end of treatment (radiographic follow-up at 6 months post-treatment)."}

Other endpoints

• {"endpoint_text":"- Evaluation of the safety and tolerability of crizotinib treatment in children with NF-2.\n- Radiographic evaluation of the persistence of crizotinib effect on the target tumor in children with NF-2 6 months after the end of treatment.","definition_or_measurement_approach":"Safety and tolerability assessed through clinical and laboratory monitoring per SmPC and protocol-specified safety assessments; radiographic evaluation as specified for imaging response and 6-month post-treatment assessment."}

Poland

Earliest CTIS Part Ii Submission Date

13-08-2024

Latest Decision Or Authorization Date

12-05-2025

Processing Time Days

272

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Medical University Of Warsaw

Organisation Type

Educational Institution

Country Of Registered Address

Poland

Third parties

• {"country":"Poland","full_name":"Cefea Sp. z o.o. sp.k.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}