E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Differentiated Thyroid Cancer |
tumore differenziato della tiroide |
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E.1.1.1 | Medical condition in easily understood language |
Thyroid Cancer |
tumore della tiroide |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 compare the efficacy of selumetinib with radioactive iodine therapy (RAI), versus placebo with RAI, by assessment of complete remission rate at 18 months post RAI treatment in the overall study population.
To compare the efficacy of selumetinib with RAI, versus placebo with RAI, by assessment of complete remission rate at 18 months post RAI treatment in a sub-group of patients with tumours known to be mutation positive for BRAF or NRAS
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Confrontare l'efficacia di selumetinib con radioiodioterapia, rispetto al placebo con radioiodioterapia in termini di valutazione del tasso di remissione completa a 18 mesi dopo il trattamento radioiodioterapico nella popolazione generale dello studio.
Confrontare l'efficacia di selumetinib con radioiodioterapia rispetto al placebo con radioiodioterapia mediante la valutazione del tasso di remissione completa a 18 mesi dopo il trattamento radioiodioterapico in un sottogruppo di pazienti con tumori noti per essere positivi alla mutazione BRAF o NRAS |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of selumetinib with RAI, versus placebo with RAI by assessment of clinical remission rate at 18 months post RAI treatment in the overall study population
To compare the efficacy of selumetinib with RAI, versus placebo with RAI by assessment of clinical remission rate at 18 months post RAI treatment in a sub-group of patients with tumours known to be mutation positive for BRAF or NRAS
To assess the safety and tolerability of selumetinib with RAI compared to placebo with RAI.
To investigate the pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered to patients with differentiated thyroid cancer.
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Confrontare l'efficacia di selumetinib con radioiodioterapia rispetto al placebo con radioiodioterapia in termini di valutazione del tasso di remissione clinica a 18 mesi dopo trattamento radioiodioterapico nella popolazione generale di studio.
Confrontare l'efficacia di selumetinib con radioiodioterapia rispetto al placebo con radioiodioterapia per la valutazione del tasso di remissione clinica a 18 mesi dopo il trattamento radioiodioterapico in un sottogruppo di pazienti con tumori noti per essere positivi alla mutazione BRAF o NRAS
Valutare la sicurezza e la tollerabilità di selumetinib con la radioiodioterapia rispetto al placebo con la radioiodioterapia.
Studiare la farmacocinetica (PK) di selumetinib e N-desmethyl selumetinib quando somministrato a pazienti con carcinoma differenziato della tiroide. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Confirmed follicular cell derived differentiated thyroid cancer
Post-surgery staging categories: primary tumour greater than 4 cm or gross extrathyroidal extension (T4 disease) or at least 1 lymph node that is 1 cm or larger or 5 or more involved lymph nodes (of any size)
Previous one or two stage total thyroidectomy with therapeutic neck dissection of metastatic lymph nodes
Patient must be suitable for radioactive iodine therapy
Patient must be suitable for TSH suppresion
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- carcinoma differenziato della tiroide derivato dalle cellule follicolari confermato istologicamente o citologicamente
- categorie di stadiazione post-chirurgica:
• tumore primario di dimensioni maggiori di 4 cm
• tumore primario di qualsiasi dimensione con estensione extratiroidea totale al di fuori della ghiandola tiroide (T4)
• N1a o N1b con almeno 1 linfonodo ≥ 1 centimetro
• N1a o N1b che coinvolge 5 o più linfonodi (di qualsiasi dimensione)
- precedente tiroidectomia totale in una o due fassi con dissezione terapeutica del collo dei linfonodi metastatici.
- paziente deve essere idoneo per la terapia radioattiva con iodio
- paziente deve essere idoneo per la soppressione con TSH |
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E.4 | Principal exclusion criteria |
Known distant metastaic disease at study entry
Diagnosis of anaplastic thyroid cancer, modullary thyroid cancer or Hurthle cell carcinoma
Presence of anti-Tg antibodies at screening
Previous treatment with 131 I (RAI) or external beam radiation therapy (EBRT)
Unresolved toxicit ≥ CTCAE Grade 2 from any previous therapy |
Conoscenza iniziale della progressione delle metastasi
Diagnosi del tumore anaplastico alla tiroide, tumore midollare alla tiroide o carcinoma cellulare….
Presenza al controllo di anticorpi anti-Tg
Precedente trattamento con 131 I (RAI) o terapia con fascio esterno (EBRT)
Tossicità irrisolte ≥ CTCAE di 2 grado da qualsiasi terapia precedente
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete remission rate in overall study population
Complete remission rate in sub-group of patients with tumours known to be mutation positive for BRAF or NRAS |
Tasso di remissione completa nella popolazione generale dello studio
Tasso di remissione completa nel sottogruppo di pazienti con tumori noti per essere positivi alla mutazione BRAF o NRAS
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Measured at 18 months post RAI treatmen |
Misurato a 18 mesi dopo radioiodioterapia |
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E.5.2 | Secondary end point(s) |
Clinical remission rate in overall study population
Clinical remission rate in sub-group of patients with tumours known to be mutation positive for BRAF or NRAS
Frequency and severity of adverse events
Assess the pharmacokinetics of selumetinib and/or N-desmethyl selumetinib by assessment of parameters including area under the curve over time (AUC) and maximum concentration |
Tasso di remissione clinica nella popolazione generale dello studio
Tasso di remissione clinica nel sottogruppo di pazienti con tumori noti per essere positivo per mutazione BRAF o NRAS
Frequenza e gravità degli eventi avversi
Valutazioni sulla farmacocinetica di selumetinib e / o selumetinib N-demetilato mediante parametri tra cui curva AUC e la concentrazione massima
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Measured at 18 months post RAI treatment
AE's Measured throughout the study until 3 years post RAI treatment
PK - In total 8 blood samples will be collected: 4 samples on pre defined time windows on Day1, and 4 samples on Day 29 or Day 30 |
Misurato a 18 mesi dopo dopo radioiodioterapia
Gli eventi avversi sono raccolti durante lo studio e fino a 3 anni dopo radioiodioterapia
PK - in totale saranno raccolti 8 campioni di sangue: 4 campioni in tempi prestabiliti al giorno 1, gli altri 4 al giorno 29 o 30. |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 | No |
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 |
Brazil |
France |
Germany |
Italy |
Poland |
Spain |
Sweden |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |