| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pediatric low-grade glioma harboring an activating RAF alteration requiring first-line systemic therapy |
| glioma pediatrico di basso grado con un’alterazione attivante di RAF che richiede una terapia sistemica di prima linea |
|
| E.1.1.1 | Medical condition in easily understood language |
| Brain tumor in children and young adults, requiring treatment for the first time |
| Tumore cerebrale nei bambini e nei giovani adulti, che richiede un trattamento per la prima volta |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10065443 |
| E.1.2 | Term | Malignant glioma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the ORR assessed per RANO criteria by independent review committee (IRC) of DAY101 monotherapy versus SoC chemotherapy in patients with pediatric low-grade glioma harboring an activating RAF alteration requiring front-line systemic therapy. |
| Confrontare l'ORR secondo i criteri RANO-LGG valutato dal comitato di revisione indipendente (IRC) di DAY101 in monoterapia rispetto alla chemioterapia standard di cura (SoC) in pazienti con glioma pediatrico di basso grado con un’alterazione attivante di RAF che richiede una terapia sistemica di prima linea. |
|
| E.2.2 | Secondary objectives of the trial |
KEY SECONDARY OBJECTIVES:
- To compare the PFS assessed by IRC of DAY101 monotherapy versus SoC chemotherapy per RANO criteria.
- To compare the duration of response (DOR) assessed by IRC of DAY101 monotherapy versus SoC chemotherapy per RANO criteria
- To compare the OS of DAY101 monotherapy versus SoC chemotherapy. |
OBIETTIVI SECONDARI CHIAVE:
- Confrontare la PFS valutata da IRC della monoterapia con DAY101 rispetto alla chemioterapia SoC secondo i criteri RANO.
- Confrontare la durata della risposta (DOR) valutata dall'IRC della monoterapia con DAY101 rispetto alla chemioterapia SoC secondo i criteri RANO.
- Confrontare la OS della monoterapia DAY101 rispetto alla chemioterapia SoC. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Less than 25 years of age with LGG with known activating RAF alteration
- Histopathologic diagnosis of glioma or glioneuronal tumor
- At least one measurable lesion as defined by RANO criteria
- Meet indication for first-line systemic therapy |
- Meno di 25 anni di età con LGG con nota alterazione RAF attivante alterazione
- Diagnosi istopatologica di glioma o tumore glioneuronale
- Almeno una lesione misurabile come definita dai criteri RANO
- Soddisfare l'indicazione per la terapia sistemica di prima linea |
|
| E.4 | Principal exclusion criteria |
- Patient has any of the following tumor-histological findings:
a) Schwannoma
b) Subependymal giant cell astrocytoma (Tuberous Sclerosis)
c) Diffuse intrinsic pontine glioma, even if histologically diagnosed as WHO Grade I-II
- Patient's tumor has additional activating molecular alterations
- Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF1/NF-2)
- Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation. |
- Il paziente presenta uno qualsiasi dei seguenti risultati istologici relativi al tumore:
a) Schwannoma
b) Astrocitoma subependimale a cellule giganti (sclerosi tuberosa)
c) Glioma pontino intrinseco diffuso, anche se diagnosticato istologicamente come di Grado I-II secondo l’OMS
- Il tumore del paziente presenta alterazioni molecolari attivanti aggiuntive
- Diagnosi nota o sospetta di neurofibromatosi di tipo 1 o 2 (NF-1/NF-2)
- Terapia antitumorale non chirurgica precedente o in corso per questa indicazione (es. chemioterapia, terapia mirata orale/EV), comprese le radiazioni. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| ORR, per RANO criteria, defined as the proportion of patients with overall confirmed response of complete response (CR) or partial response (PR). |
| ORR, in base ai criteri RANO, definita come la proporzione dei pazienti con risposta complessiva confermata della risposta completa (CR) o risposta parziale (PR) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After the last patient has been followed up for 12 months (anticipated to occur at approximately 36 months after first patient enrolled). |
| Dopo che l'ultimo paziente è stato seguito per 12 mesi (si prevede che ciò avvenga a circa 36 mesi dal primo paziente arruolato) |
|
| E.5.2 | Secondary end point(s) |
- PFS per RANO criteria, defined as time from randomization to PD or death from any cause.
- DOR per RANO criteria, defined as time from confirmed response (CR, PR) to PD or death from any cause for patients with confirmed response.
- OS, defined as time from randomization up to death from any cause.
- Adverse events, vital signs, laboratory parameters.
- Change from baseline in Adaptive Behavior Composite ABS, Motor Skills Domain, Daily Living Domain, Socialization Domain, and Communication Domain Scores from the VABS by semi-structured telephone interview at 1, 2, and 5 years.
- Change in age-adjusted visual acuity (AVA), best corrected visual acuity (BCVA), and visual progression-free survival (V-PFS) defined as the time from start of treatment to visual event (blindness or VA loss) in one eye for OPG patients aged> = 3 years.
- ORR, defined as the proportion of patients with overall confirmed response per RANO.
- ORR, defined as the proportion of patients with overall confirmed response per RAPNO.
- CBR, defined as the proportion of patients with radiological tumor stabilization or regression per RANO or RAPNO criteria, as applicable.
- Measured by the time to first response following initiation of therapy in patients with best overall confirmed response per RANO or RAPNO criteria, as applicable.
- PFS per RANO or RAPNO (as applicable), defined as time from randomization to PD or death from any cause.
DOR, defined as time from confirmed response to PD or death from any cause for patients with confirmed response per RANO or RAPNO criteria, as applicable. |
- PFS in base ai criteri RANO, definito come il tempo dalla randomizzazione a PD o morte per qualsiasi causa
- DOR in base ai criteri RANO, definito come il tempo dalla risposta confermata (CR, PR) a PD o morte per qualsiasi causa per pazienti con risposta confermata
- OS definito come il tempo dalla randomizzazione fino alla morte per qualsiasi causa
- Eventi avversi, segni vitali, parametri di laboratorio
- Cambi dal basale nelle Adaptive Behavior Composite ABS, Motor Skills Domain, Daily Living Domain, Socialization Domain, and Communication Domain Scores da VABS mediante una intervista telefonica semi strutturata all’anno 1,2 e 5
- Cambio nella acuità visiva corretta per l'età (AVA), acuità visiva meglio corretta (BCVA) e sopravvivenza libera da progressione visiva (V-PFS) definita come il tempo trascorso dall'inizio del trattamento all'evento visivo (cecità o perdita di VA) in un occhio per i pazienti OPG di età >= 3 anni.
- ORR definita come la proporzione dei pazienti con risposta complessiva confermata per RANO
- ORR definita come la proporzione dei pazienti con risposta complessiva confermata per RAPNO
- CBR definita come la proporzione dei pazienti con stabilizzazione radiologica del tumore or regressione per i criteri di RANO o RAPNO, come applicabile
- Misurato dal tempo alla prima risposta dopo l'inizio della terapia nei pazienti con la migliore risposta globale confermata secondo i criteri RANO o RAPNO, come applicabile
- PFS secondo i criteri RANO o RAPNO (come applicabile), definito come il tempo dalla randomizzazione alla PD o alla morte per qualsiasi causa.
DOR definito come il tempo dalla risposta confermata a PD o alla morte per qualsiasi causa per i pazienti con risposta confermata secondo i criteri RANO o RAPNO, a seconda dei casi. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Up to 60 months |
| fino a 60 mesi |
|
| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability |
| tollerabilità |
|
| 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) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 49 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Israel |
| Korea, Republic of |
| New Zealand |
| Singapore |
| Taiwan |
| United States |
| Austria |
| Finland |
| France |
| Sweden |
| Netherlands |
| Spain |
| Switzerland |
| Czechia |
| Germany |
| Greece |
| Italy |
| Belgium |
| Denmark |
| Hungary |
| Ireland |
| Norway |
| Slovenia |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 7 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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