E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PATIENTS WITH BRAIN TUMOR RELATED EPILEPSY |
PAZIENTI CON EPILESSIA SECONDARIA A NEOPLASIA CEREBRALE |
|
E.1.1.1 | Medical condition in easily understood language |
PATIENTS WITH BRAIN TUMOR RELATED EPILEPSY |
PAZIENTI CON EPILESSIA SECONDARIA A NEOPLASIA CEREBRALE |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068330 |
E.1.2 | Term | Symptomatic epilepsy |
E.1.2 | System Organ Class | 100000004852 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of LCM treatment on seizure control as add-on in patients with brain tumor-related epilepsy, after 6 months period of treatment. |
Valutare l’effetto del trattamento con lacosamide in add-on sul controllo delle crisi epilettiche correlate a neoplasia cerebrale durante 6 mesi di trattamento |
|
E.2.2 | Secondary objectives of the trial |
1. Responder rate ≥50%, 75%, 100%
2. To monitor the impact on QoL, on mood and on functional status at 3 and 6 months as compared with baseline
3. To evaluate the possible modifications of blood levels of LCM
4. To evaluate the occurrence of adverse events during therapy with LCM using Adverse Events Profile (AEP)
|
Valutare l’impatto del trattamento con lacosamide in add-on sulla qualità di vita, sull’umore e sul functional status a 3 e a 6 mesi.
o Valutare le eventuali modificazioni plasmatiche di lacosamide durante il trattamento.
o Valutare l’incidenza di eventi avversi durante il trattamento con lacosamide
mediante un test di valutazione degli effetti avversi specifico per pazienti in
trattamento con AEDs.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients Age ≥18 years ≤75 (both sexes) with primary BT (astrocytoma II and III WHO, oligodendroglioma II and III WHO and multiform glioblastoma), cerebral lymphoma, with previous surgical resection or biopsy.
Informed consent signature
Patients in a stable phase of disease (evidenced by unchanged neuroradiological examinations).
Symptomatic epilepsy characterized by partial seizures with or without secondary generalization; ≥ 2 seizure in the last month, despite treatment with the maximum tolerated stable dose of 1-2 AED.
Seizure retrospective count at least in the last 28 days.
Patients could be also in treatment with CT, radiotherapy and corticosteroids started before LCM introduction not generating specific adverse effects.
Patients treated for the oncological disease following international oncological guidelines
|
): pazienti con neoplasia cerebrale con crisi parziali farmacoresitenti, di età compresa tra i 18 ed i 75 anni, con neoplasia cerebrale primitiva (astrocitoma II e III WHO, oligodendroglioma II e III WHO e glioblastoma multiforme), linfoma cerebrale sottoposti precedentemente a resezione chirurgica o a biopsia. I pazienti potranno essere in trattamento chemioterapico concomitante e/o in terapia corticosteroidea. Tutti i pazienti devono essere in fase di stabilità di malattia come evidenziato dalle neuroimmagini.
Le crisi parziali con o senza secondaria generalizzazione devono essere farmaco resistenti e in numero di almeno 2 episodi nel mese precedente.
|
|
E.4 | Principal exclusion criteria |
Patients Age ≤18 years ≥75 (both sexes) with primary BT
Karnofsky Performace Status <60
Patients with a previous epilepsy before tumor onset
Patients with other chronic neurological and psychiatric diseases
Patients with brain metastases
Patients child bearing or breastfeeding
Allergy or intolerance to soya, peanuts, lacosamide, lacosamide tablet eccipients.
Patients with known preexisting second or third degree AV block.
|
Età <18 anni>75
Karnofsky Performance Status <60
Pazienti con epilessia non secondaria
Pazienti affetti da qualunque altra patologia neurologica o psichiatrica
Pazienti con metastasi cerebrali
Pazienti in gravidanza o allattamento
Pazienti intolleranti alla soya, noccioline, lacosamide, o agli eccipienti delle compresse di LCM. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Mean seizure frequency reduction as compared with baseline period available during the 6 months of treatment period after having reached minimal effective dose of 200mg/day. |
Riduzione della frequenza media di crisi al follow-up finale rispetto al tempo 0 (baseline) dopo aver raggiunto la minima dose efficace di lacosamide di 200mg/die. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Seizure freedom rate at 6 months of treatment period.
Responder rate using a ≥ 50% and 75% reduction of seizure frequency as compared with baseline. A patient responder is defined as a patient having achieved at least a 50% monthly seizure reduction during the six months of treatment as compared with seizure frequency at baseline. Seizure frequency will be evaluated as mean of the seizure frequency during the 6 months of the treatment period.
Stability of blood levels of LCM during the follow-up.
|
Libertà di crisi a 3 e 6 mesi di trattamento.
_ Responder Rate del ≥ 50% e del 75% di riduzione della frequenza media di crisi
rispetto al tempo 0 (baseline). La frequenza delle crisi sarà valutata come media
della frequenza crisi durante i 6 mesi di follow-up.
_ Stabilità dei livelli ematologici di LCM durante il follow-up
_ Effetto di lacosamide sulla qualità di vita valutata utilizzando il QOLIE 31-P (10) e
l’Eortc QLQ-C30 (11).
_ Effetto di lacosamide sul tono dell’umore utilizzando la Zung Self Depression Rating
Scale (12).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 19 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 19 |