E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
carcinoma of the oral cavity and oropharynx |
neoplasia del cavo orale e orofaringe |
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E.1.1.1 | Medical condition in easily understood language |
Progressive disease (relapse on T and N0) in the oral cavity and oropharynx |
Malattia progressiva (recidiva sul T ed N0) nel cavo orale e orofaringe |
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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 |
Superiority of the treatment of Electrochemotherapy with Bleomycin in terms of objective response compared to treatment with cetuximab + therapy based on platinum + 5-fluorouracil |
Superiorità del trattamento di Elettrochemioterapia con Bleomicina in termini di risposta oggettiva rispetto al trattamento con cetuximab + terapia a base di platino + 5-fluorouracile |
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E.2.2 | Secondary objectives of the trial |
1. Overall survival; 2. Evaluation of progression free survival time; 3. Evaluation of the duration of the response (the time from the first documentation of a complete or partial response until the first occurrence of disease progression or until death); 4. Evaluation of disease control, defined as complete response, partial response and stable disease between the two groups; 5. The quantification of the impact of treatment on the patient's quality of life, in terms of pain reduction and bleeding (EORTC QLQ-C30, EORTC QLQ-H&N35, EQ-5D-5L).
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1. Overall survival 2. Valutazione del tempo di progressione libera da malattia tra i due gruppi 3. Valutazione della durata della risposta intesa come il tempo dalla prima documentazione di risposta completa o parziale fino alla prima occorrenza di progressione di malattia o morte 4. Valutazione del controllo della malattia, inteso come risposta completa, risposta parziale e malattia stabile, tra i due gruppi 5. Valutazione della qualità di vita (EORTC QLQ-C30, EORTC QLQ-H&N35, EQ-5D-5L) con particolare attenzione all’effetto sul dolore e sul sanguinamento, tra i due gruppi
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age> 18 yrs; 2. Progressive disease (recurrence on T and N0) of oral cavity or oropharynx 3. Histologically verified squamous cell carcinoma; 4. Measurable lesions suitable for application of electric pulses; 5. Performance status (Karnofsky ≥ 70; WHO ≤ 2); 6. Life expectancy> 3 months; 7. Patients must be mentally capable of understanding the information given and sign informed consent; 8. Patients must have offered standard treatments.
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1. Età > 18 anni 2. Malattia progressiva (recidiva sul T ed N0) nel cavo orale e orofaringe 3. Conferma istologica di carcinoma squamoso testa collo 4. Lesioni misurabili adatte per l'applicazione di impulsi elettrici 5. Performance status (Karnofsky ≥ 70; WHO ≤ 2) 6. Aspettativa di vita> 3 mesi 7. Pazienti in grado di comprendere il tipo di trattamento che riceveranno ed in grado di firmare il consenso informato 8. Pazienti che rifiutano altri trattamenti
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E.4 | Principal exclusion criteria |
1. Age<18 yrs; 2. Other symptomatic lesions not under control; 3. Lesions not suitable for ECT (bony invasion, large vessels infiltration, etc.); 4. Injectable lesions for systemic treatment with cetuximab + platinum + 5-fluorouracil therapy 5. Acute lung infection; 6. Symptoms of poor lung function; 7. Non correctable severe coagulation disorders; 8. Previous allergic reactions to bleomycin; 9. Previous cumulative dose of 250 mg/m2 of bleomycin exceeded; 10. Chronic renal dysfunction (creatinine> 150 µmol/L must be considered a lower administered dose of bleomycin) 11. Any severe and uncontrolled systemic illness 12. Pregnancy or lactation **;
** Pregnancy has been established before enrollment by beta-hCG on urine (pregnancy test or urinary beta-HCG) or on blood (plasma beta-hCG)
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1. Età inferiore ai 18 anni 2. Altre lesioni sintomatiche fuori controllo 3. Lesioni non candidabili all’ECT (invasione dell’osso, infiltrazione grandi vasi, etc.) 4. Lesioni non candidabili a trattamento sistemico con cetuximab + terapia a base di platino + 5-fluorouracile 5. Infezione polmonare acuta 6. Scarsa funzionalità polmonare o funzionalità anomala 7. Disordini importanti della coagulazione 8. Allergia alla bleomicina 9. Dosi cumulative di 250 mg/m2 di bleomicina ricevuta 10. Disfunzione renale cronica (creatinina> 150 µmol/L) 11. Qualsiasi malattia sistemica grave e incontrollata 12. Gravidanza o allattamento**
**Lo stato di gravidanza è stato accertato prima dall'arruolamento tramite il dosaggio della Beta-hCG sulle urine (Test di gravidanza o beta-HCG urinaria) o sul sangue (beta-hCG plasmatica)
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E.5 End points |
E.5.1 | Primary end point(s) |
To verify if the treatment with ECT and Bleomycin is superior in terms of objective response to treatment with cetuximab + therapy based on platinum + 5 fluorouracil. |
Per verificare se il trattamento con ECT e Bleomicina è superiore in termini di risposta obiettiva al trattamento con terapia con cetuximab + a base di platino + 5 fluorouracile. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The clinical response will be evaluated by RECIST 1.1 criteria on CT and/or MR images at 2 months from baseline. |
La risposta clinica sarà valutata secondo i criteri RECIST 1.1 su immagini TC e / o RM a 2 mesi dal basale. |
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E.5.2 | Secondary end point(s) |
1. Overall survival; 2. Evaluation of progression free survival time; 3. Evaluation of the duration of the response (the time from the first documentation of a complete or partial response until the first occurrence of disease progression or until death); 4. Evaluation of disease control, defined as complete response, partial response and stable disease between the two groups; 5. The quantification of the impact of treatment on the patient's quality of life, in terms of pain reduction and bleeding (EORTC QLQ-C30, EORTC QLQ-H&N35, EQ-5D-5L).
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1. Overall survival 2. Valutazione del tempo di progressione libera da malattia tra i due gruppi 3. Valutazione della durata della risposta intesa come il tempo dalla prima documentazione di risposta completa o parziale fino alla prima occorrenza di progressione di malattia o morte 4. Valutazione del controllo della malattia, inteso come risposta completa, risposta parziale e malattia stabile, tra i due gruppi 5. Valutazione della qualità di vita (EORTC QLQ-C30, EORTC QLQ-H&N35, EQ-5D-5L) con particolare attenzione all’effetto sul dolore e sul sanguinamento, tra i due gruppi
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• CT, MR or PET / CT control at 2 months, 6 months and 12 months after treatment
• Blood sampling including CD8 / CD16 assay at 1, 2, 4, 6 months as per normal clinical practice
• Quality of life assessment will be at each follow-up visit |
• CT, MRI o PET/TC di controllo a 2 mesi, 6 mesi ed a 12 mesi dal trattamento
• Prelievi ematici incluso dosaggio CD8/CD16 a 1, 2, 4, 6 mesi come da normale pratica clinica
• La valutazione della qualità della vita sarà effettuata ad ogni visita di follow-up |
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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 | No |
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) | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
terapia sistemica |
systemic therapy |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
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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 | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 48 |