E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic or unresectable papillary thyroid cancer positive for BRAF V600 mutation and resistant to radioactive iodine therapy |
Cancro papillare della tiroide metastatico o non resecabile positivo al BRAF V600 e resistente alla terapia allo iodio radioattivo |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033701 |
E.1.2 | Term | Papillary thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 best overall response rate (BORR) (complete + partial response) in Cohort 1 (TKI-naïve patients). − BORR will be based on investigator assessment, based on the findings on computed tomography (CT) or magnetic resonance imaging, using RECIST 1.1 |
Valutare il miglior tasso di risposta complessiva (BORR) (risposta completa + parziale) nella coorte 1 (pazienti naïve alla tirosin Kinasi-TKI). – Il BORR si basera' sulla valutazione dello sperimentatore, in base alle informazioni relative agli esami di tomografia computerizzata (TC) o di risonanza magnetica per immagini, usando RECIST 1.1 |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate clinical benefit rate (CBR) in TKI naïve patients 2. To further assess efficacy of Vemurafenib using the following secondary variables: duration of response, progression free survival (PFS), and overall survival (OS) in TKI-naïve patients 3. To evaluate the efficacy (BORR, CB, duration of response, PFS, and OS) in TKI-exposed patients 4. To evaluate the tolerability and safety profile of Vemurafenib using the NCI CTCAE (version 4.0) in both TKI-naïve and TKI treated patients 5. To characterize the pharmacokinetic (PK) profile of Vemurafenib in patients with thyroid cancer |
1. Valutare il grado di beneficio clinico (CBR) nei pazienti naïve a TKI 2. Valutare ulteriormente l’efficacia di Vemurafenib usando le seguenti variabili secondarie: durata della risposta, sopravvivenza libera da progressione (PFS), e sopravvivenza complessiva (OS) in pazienti naïve a TKI 3. Valutare l’efficacia (BORR, CB, durata della risposta, PFS, e OS) in pazienti esposti a TKI 4. Valutare il profilo di tollerabilita' e di sicurezza di Vemurafenib usando NCI CTCAE (versione 4.0) sia in pazienti naïve a TKI che in quelli trattati con TKI 5. Caratterizzare il profilo farmacocinetico (PK) di vemurafenib in pazienti con carcinoma della tiroide |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients >/= 18 years of age - Metastatic or unresectable papillary thyroid cancer for which standard curative or palliative measures do not exist or are no longer effective - Positive for BRAF V600 mutation (Roche Cobas 4800 BRAF V600 Mutation Test) - Radioactive Iodine resistant disease - Prior therapy excluding (Cohort 1) or including (Cohort 2) tyrosine kinase inhibitor with activity against VEGFR2 - Clinically relevant disease progression according to RECIST criteria within the prior 14 months - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate hematological, renal and liver function |
- Pazienti adulti >/= 18 anni di eta' - Cancro papillare tiroideo metastatico o non asportabile chirurgicamente per cui non esistono o non sono piu' efficaci i trattamenti standard di cura o palliativi NOTA: potranno essere arruolati quei pazienti i cui carcinomi mostrano aree di “altra istologia”, a condizione che l’istologia del carcinoma rimanga prevalentemente di tipo papillare. Si potra' discutere con il Medical Monitor se vi sono domande riguardanti l’ammissibilita' di pazienti, i cui carcinomi presentino un’istologia “mista”.- Positivita' per la mutazione BRAF V600 (Roche Cobas 4800 BRAF V600 Mutation Test) - Patologia resistente allo iodio radioattivo - Terapia precedente che escluda (Coorte 1) o includa (Coorte 2) sorafenib e trattamento con inibitore della tirosin-chinasi - Progressione della patologia clinicamente rilevante in accordo ai criteri RECIST entro i 14 mesi precedenti - Stato di performance Eastern Cooperative Oncology Group (ECOG) di 0 o 1 - Adeguate funzionalita' ematologiche, renali ed epatiche |
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E.4 | Principal exclusion criteria |
- Histological diagnosis other than papillary thyroid carcinoma (PTC), including squamous cell variants of PTC or PTC with areas of squamous metaplasia - Active or untreated CNS metastases or previous whole brain irradiation - History of or known carcinomatous meningitis - Anticipated or ongoing administration of any anti-cancer therapies other than those administered in the study - Active squamous cell skin cancer that has not been excised or adequately healed post excision - Previous treatment with any agent tat specifically and selectively targets the MEK or BRAF pathway - Prior radiotherapy to the only measurable lesion - Clinically relevant cardio-vascular disease or event within the prior 6 months |
- Diagnosi istologica diversa da carcinoma papillare tiroideo (PTC), incluse le varianti del PTC a cellule squamose o PTC con aree di metaplasie squamose - Metastasi al CNS attive o non trattate - Storia o conoscenza di meningite carcinomatosa - Somministrazione in corso o anticiapta di qualsiasi terapia anti-cancro diverse da quelle somministrate nello studio - Cancro della pelle a cellule squamose attivo, non rimosso chirurgicamente o guarito in modo adeguato dopo la rimozione - Trattamenti precedenti con un qualsiasi agente che mira selettivamente e specificatamente il pathway di MEK o BRAF - Radioterapia precedente sull`unica lesione misurabile - Patologie cardio-vascolari clinicamente rilevanti o eventi entro i sei mesi precedenti |
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E.5 End points |
E.5.1 | Primary end point(s) |
Best overall response rate (BORR) in TKI-naive patients (Cohort 1), assessed by the investigator according to RECIST criteria |
Tasso di migliore risposta globale (BORR) nei pazienti naive a TKI (Coorte 1), valutato dallo sperimentatore in accordo con i criteri RECIST |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Clinical benefit rate (objective response rate + stable disease) in TKI-naive patients 2. Duration of response in TKI-naive patients 3. Progression-free survival in TKI-naive patients 4. Overall survival in TKI-naive patients 5. Best overall response rate in TKI-exposed patients (Cohort 2) 6. Clinical benefit rate in TKI-exposed patients 7. Duration of response in TKI-exposed patients 8. Progression-free survival in TKI-exposed patients 9. Overall survival in TKI-exposed patients 10. Safety: Incidence of adverse events 11. Pharmacokinetics (Tmax, Cmax, Cmin, AUC) |
1. Tasso di beneficio clinico (tasso di risposta obiettivo + malattia stabile) nei pazienti naive per TKI 2. Durata della risposta nei pazienti naive per TKI 3. Sopravvivenza libera da malattia nei pazienti naive per TKI 4. Sopravvivenza globale nei pazienti naive per TKI 5. Miglior tasso di risposta nei pazienti esposti a TKI (Coorte 2) 6. Tasso di benefico clinico nei pazienti esposti a TKI 7. Durata della risposta nei pazienti esposti a TKI 8. Sopravvivenza libera da malattia nei pazienti esposti a TKI 9. Sopravvivenza globale nei pazienti esposti a TKI 10. Sicurezza: incidenza degli eventi avversi 11. Farmacocinetica (Tmax, Cmax, Cmin, AUC) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: 18 months 2. Time Frame: 4.5 years 3. Time Frame: 4.5 years 4. Time Frame: 4.5 years 5. Time Frame: 18 months 6. Time Frame: 18 months 7. Time Frame: 4.5 years 8. Time Frame: 4.5 years 9. Time Frame: 4.5 years 10. Time Frame: 4.5 years 11. Time Frame: 4.5 years |
1. Finestra temporale: 18 mesi 2. Finestra temporale: 4.5 anni 3. Finestra temporale: 4.5 anni 4. Finestra temporale: 4.5 anni 5. Finestra temporale: 18 mesi 6. Finestra temporale: 18 mesi 7. Finestra temporale: 4.5 anni 8. Finestra temporale: 4.5 anni 9. Finestra temporale: 4.5 anni 10. Finestra temporale: 4.5 anni 11. Finestra temporale: 4.5 anni |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 |
Samples for BRAF V600 testing, exploratory biomarkers, Roche Clinical Repository, tolerability |
Test di campioni di BRAF V600, biomarcatori esplorativi, Roche Clinical Repository, tollerabilita' |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
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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
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The study will end when all patients have completed at least 6 months of follow up after discontinuation of study drug. |
Lo studio terminera' quando tutti i pazienti avranno completato almeno 6 mesi di followup dopo l'interruzione del farmaco sperimentale. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 37 |
E.8.9.2 | In all countries concerned by the trial days | 0 |