epilepsy, mTORopathies, focal cortical dysplasia, LEATS
Conditions
Sponsors
The Children's Memorial Health Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age at inclusin from 4 months to 18 years. 2. Diagnosis of drug-resistant epilepsy as defined by ILAE (Kwan 2010), with focal onset (ICD-10: G40.2), with confirmed coexistence or suspicion of mTORopathy in MRI, including: FCD, hemimegalencephaly, LEATs; active epilepsy at study entry, at least 8 seizures in the prior 4 weeks prior to study entry 3. Informed consent to the participation in the study by the patient's legal caregivers and the patient himself, if he is 13 years of age or older. 4. Negative result of the pregnancy test performed within 2 weeks prior to the start of the study in patients of reproductive age. 5. Written consent to the use of effective contraception in sexually active patients or an obligation to abstaining from sexual activity during and for 3 months after its treatment. Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Severe coexisting diseases, e.g. renal failure, immunodeficiency, 2. Clinically significant disease of the cardiovascular system, e.g. arrhythmia, 3. Earlier diagnosis of neoplasm <5 years requiring antitumor treatment, 4. Active infection requiring general treatment, 5. Contraindications to use, including the inability to take or known hypersensitivity to the drug used in the study, 6. Simultaneous administration of drugs that are strong inhibitors of CYP3A or PgP, 7. Radiological features of active CNS bleeding except for asymptomatic resolving changes after biopsy or point bleeding in the tumor, 8. Major surgery, open biopsy <28 days prior to treatment initiation, 9. Minor surgical procedures <2 days before the start of treatment, e.g. implantation of a vascular port, 10. Non-healing wound, unhealed fracture, 11. Radiation therapy of the CNS <28 days, 12. Pregnancy, breastfeeding, 13. Active participation in another research program or completed <30 days, 14. Systemic treatment with an mTOR inhibitor from other indications in the 3 months preceding study enrollment, 15. Use of marijuana or its derivatives 16. Live vaccine intake <6 weeks prior to study inclusion, 17. Receipt of inactivated vaccine or mRNA vaccine <4 weeks prior to study inclusion. 18. Tuberous sclerosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine safety and tolerability of rapamycin in a drug resistant epilepsy associated with rare and ultra-rare diseases of the central nervous system associated with the activation of the mTOR pathway;Secondary Objective: The secondary aim of the study is to ascertain the antiseizure efficacy of rapamycin in a drug resistant epilepsy associated with rare and ultra-rare diseases of the central nervous system associated with the activation of the mTOR pathway;Primary end point(s): The primary safety endpoint of rapamycin will be the assessment of the incidence of adverse reactions (according to the CTCAE classification) during the treatment phase and follow-up of patients with drug-resistant epilepsy The primary efficacy endpoint will be the proportion of patients achieving a =50% reduction in seizures ;Timepoint(s) of evaluation of this end point: -interim analysis -final analyses after the formal final database lock, planned within one month after the last patient last visit in the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A secondary safety endpoint will be the CTCAE severity of adverse reactions and the number of patients experiencing adverse reactions requiring exclusion from the study or premature termination of participation during the therapeutic dose period. The effect of treatment on the results of laboratory tests will also be analyzed. The secondary endpoint of the trial will be maintenance of short-term effects, improvement of quality of life in =50% of patients / families. ;Timepoint(s) of evaluation of this end point: -interim analysis -final analyses after the formal final database lock, planned within one month after the last patient last visit in the study | — |
Countries
Poland
Contacts
Public ContactKrzysztof Sadowski
The Children's Memorial Health Institute
Outcome results
None listed