E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
primary cutaneous melanoma |
melanoma cutaneo primario ad alto rischio di recidiva |
|
E.1.1.1 | Medical condition in easily understood language |
primary cutaneous melanoma |
melanoma cutaneo primario ad alto rischio di recidiva |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027155 |
E.1.2 | Term | Melanoma skin |
E.1.2 | System Organ Class | 100000004864 |
|
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 rate of complications, defined as grade =3 adverse events [according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute (NCI-CTCAE) version 5.0], of surgical excision margins compared to Electrochemotherapy in patients with cutaneous melanoma after the primary tumor excission. |
Valutare, nei pazienti affetti da melanoma primario della cute già asportato chirurgicamente, il tasso di complicanze definite come eventi avversi di grado = 3 [secondo il Common Terminology Criteria for Adverse Events of the National Cancer Institute (NCI-CTCAE) versione 5.0], dell’ escissione chirurgica dei margini rispetto all’Elettrochemioterapia (ECT). |
|
E.2.2 | Secondary objectives of the trial |
To compare the two arm in terms of: • Quality of life [(European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30; EuroQol five-dimensional(EQ-5D-5L) and Derriford Appearance Scale (DAS 24) questionnaires] • Costs • Pain Assessment [Visual Analogue Scale (VAS)] • Local recurrence rate (defined as the combination of local recurrence, in transit recurrence and regional node metastasis) • Disease-free survival |
Confrontare i due bracci di trattamento in termini di:
• Qualità di Vita (EORTC QLQ-C30; EQ-5D-5L; DAS 24 questionari) • Dolore (Scala VAS) • Costi • Tasso di recidiva locale, (definito come la combinazione di recidiva locale, recidiva in transit e metastasi ai linfonodi regionali) • Disease-free survival |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age = 18 years Histologically confirmed diagnosis of cutaneous melanoma Stage of disease: single, primary, localized cutaneous melanoma 2 mm or greater in thickness Breslow on the trunk or limbs (excluding soles of the feet) Performance status (PS) according to The Eastern Cooperative Oncology Group (ECOG) = 2 Written informed consent Use of an acceptable mean of contraception for men and women of childbearing potential |
Diagnosi istologica di melanoma cutaneo primitivo Tumore primitivo con spessore < 2 cm secondo Breslow, localizzato agli arti o al tronco (esclusa pianta del piede) asportato chirurgicamente. Età = 18 Performance status (PS) 0-1 secondo ECOG Metodi contraccettivi efficaci adottati sia dagli uomini che dalle donne nei casi in cui esiste la possibilità di un concepimento Consenso informato scritto |
|
E.4 | Principal exclusion criteria |
• Diagnosis of mestastatic melanoma. • Serious coagulation abnormality, INR above 1.5 • Absolute neutrophil count below 1,000/ml • Platelet count below 70,000/ml • Hemoglobin = 9 gr/dl • Known allergies to Bleomycin • Cumulative lifetime dose of Bleomycin exceeding 250 mg/m2 • Peripheral neuropathy greater than grade 2 • Chronic renal deficiency (creatinine>1.5 µg/L) • Active infection • Cardiac arrhythmias [e.g., significant ventricular arrhythmia such as persistent ventricular tachycardia and/or ventricular fibrillation; severe conduction disorders as atrioventricular block 2 and 3, sinoatrial block] • Epilepsy • Pregnant or breastfeeding • Any other cancer from which the patients had been disease free for less than 5 years (except treated and cured basal–cell or squamous-cell skin cancer, superficial bladder cancer, or treated carcinoma in situ of the cervix, breast, or bladder) • Pulmonary infection • Severely impaired lung function |
¿ Diagnosi di melanoma metastatico ¿ Coagulopatie con INR >1.5 ¿ Funzione osteomidollare inadeguata: Neutrofili < 1000/mm3 Conta piastrinica < 70.000/ mm3 Emoglobina <9 g/dl ¿ Allergia nota alla Bleomicina ¿ Dose cumulativa di Bleomicina superiore a 250 mg/m2
¿ Neuropatia periferica Neuropatia periferica sintomatica di grado >2 secondo NCI CTCAE v.5.0. ¿ Livelli di creatinina sierica >1.5 LSN ¿ Infezioni in atto ¿ Storia di aritmia cardiaca (es. aritmia ventricolare come tachicardia ventricolare persistente e/o fibrillazione ventricolare; disturbi severi della conduzione tipo bloccoa atrio ventricolare di secondo e terzo grado, blocco seno atriale) ¿ Epilessia ¿ Gravidanza o allattamento ¿ Diagnosi di altra neoplasia nei 5 anni precedenti la randomizzazione, ad eccezione dei tumori baso cellulare o squamo cellulari della cute, del carcinoma superficiale della vescica, non muscolo invasivo, o del carcinoma in situ della cervice, della mammella e della vescica trattati). ¿ Infezioni polmonari ¿ Funzione polmonare gravemente compromessa ¿ Qualunque altra patologia concomitante o alterazione degli esami di laboratorio o farmaco concomitante che potrebbe controindicare l’uso dei farmaci in studio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• To evaluate the rate of complications, defined as grade =3 adverse events [according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute (NCI-CTCAE) version 5.0], of surgical excision margins compared to Electrochemotherapy in patients with cutaneous melanoma after the primary tumor excission. |
Valutare, nei pazienti affetti da melanoma primario della cute già asportato chirurgicamente, il tasso di complicanze definite come eventi avversi di grado = 3 [secondo il Common Terminology Criteria for Adverse Events of the National Cancer Institute (NCI-CTCAE) versione 5.0], dell’ escissione chirurgica dei margini rispetto all’Elettrochemioterapia (ECT). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1 Quality of life [(European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30; EuroQol five-dimensional(EQ-5D-5L) and Derriford Appearance Scale (DAS 24) questionnaires] 2 Costs 3 Pain Assessment [Visual Analogue Scale (VAS)] 4 Local recurrence rate (defined as the combination of local recurrence, in transit recurrence and regional node metastasis) 5 Disease-free survival |
1 Qualità di Vita (EORTC QLQ-C30; EQ-5D-5L; DAS 24 questionari) 2 Dolore (Scala VAS) 3 Costi 4 Tasso di recidiva locale, (definito come la combinazione di recidiva locale, recidiva in transit e metastasi ai linfonodi regionali) 5 Disease-free survival |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 -Questionnaires must be compiled by the patients before any study procedure but within 30 days prior to randomization (Visit 1, baseline) and at pre -treatment visit (Visit 2, Day -1), at wound evaluation visits (Visit 4, Day 1 and Visit 5, Day 15) and at follow-up visit (Visit 6, non more than 30 calendars days after treatment) in both treatment arms. 3 -Questionnaires must be compiled by the patients before any study procedure but within 30 days prior to randomization (Visit 1, baseline) and at pre -treatment visit (Visit 2, Day -1), treatment visit (visit 3, Day0) at wound evaluation visits (Visit 4, Day 1 and Visit 5, Day 15) and at follow-up visit (Visit 6, non more than 30 calendars days after treatment) in both treatment arms. 4 -after 1 month |
1-Tali questionari dovranno essere compilati prima della randomizzazione (Basale, Visita 1), e poi successivamente in tutte le successive visite schedulate come indicato Tabella 1 (Day-1 Visita 2; Day 1 Visita 4; Day 15 Visita 5; Day 30 Visita 6). 3-Tale scala dovrà essere compilata prima della randomizzazione (Basale, Visita 1), e poi successivamente in tutte le successive visite schedulate come indicato Tabella 1 (Day-1 Visita 2; Day 0 visita3; Day 1 Visita 4; Day 15 Visita 5; Day 30 Visita 6). 4 - dopo 1 mese |
|
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 | No |
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
chirurgia dei margini |
margins excission |
|
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 | 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 | Information not present in EudraCT |
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 | 3 |
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 | 3 |
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 |