E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ulcerated primary cutaneous melanoma >1mm |
Ulcerated primary cutaneous melanoma >1mm (T2b-4bN0M0) |
|
E.1.1.1 | Medical condition in easily understood language |
Ulcerated primary cutaneous melanoma >1mm |
Ulcerated primary cutaneous melanoma >1mm |
|
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 | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the trial is to prospectively assess the efficacy, toxicity, quality of life with PEF IFN alfa-2b as compared to observaton after adequate surgery for ulcerated primary cutaneous melanomas with T(2-4)bN0M0. The primary objective is to determine whether post-operative adjuvant therapy with PEG IFN alfa-2b improves relapse-free survival (PFS) as compared to observation. |
Valutazione prospettica dell'efficacia, della tossicità e della qualità della vita con peginterferone alfa-2b rispetto all'osservazione a seguito di intervento chirurgico adeguato per pazienti con <csf style="Bold" bold="on">melanoma primitivo cutaneo i ulcerato con T(2-4)bN0M0</csf> |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are :
-To compare adverse event profiles between patients receiving PEG IFN alfa-2b versus patients in the observation arm
-To determine whether post-operative adjuvant therapy with PEG IFN alfa-2b improves overall survival (OS) as compared to observation
-To determine whether post-operative adjuvant therapy with PEG IFN alfa-2b improves distant metastases-free survival (DMFS) as compared to observation
-To compare quality of life between the two arms (PEG IFN alfa-2b versus observation) |
Gli obiettivi secondari sono:
-Per confrontare i profili degli eventi avversi tra i pazienti trattati con PEG IFN alfa-2b rispetto ai pazienti nel gruppo di osservazione
-Per determinare se terapia post-operatoria adiuvante con PEG IFN alfa-2b migliora la sopravvivenza generale (OS) rispetto alla sola osservazione
-Per determinare se la terapia post-operatoria adiuvante con PEG IFN alfa-2b migliora metastasi distanti sopravvivenza libera (DMF) rispetto all'osservazione
-Per confrontare la qualità della vita tra i due bracci (PEG IFN alfa-2b rispetto osservazione) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Subjects must have histologically documented ulcerated primary cutaneous melanoma with a Breslow thickness >1mm that has been excised radically 3 months prior to randomization. Excision margins of at least 1cm are required. In the head and neck areas and in case of locations distally on extremities narrower margins are acceptable as long as they are radical.
-In case subjeccts have undergone Sentinel Node staging after the excision of the primary, this must be done within the time frame of 3 months between the date of final excision of the primary and the date of randomization.
-Subjects must have an ECOG performance status of 0 or 1.
-Subjects must be between 18-70 years old.
-Subjects must have adequate hepatic, renal and bone marrow function as defined by the following parameters obtained within 4 weeks prior to initiation of study treatment.
-Subjects must give informed consent according to ICH-GCP or national/local policy. |
-I soggetti devono essere istologicamente documentato ulcerate melanoma cutaneo primario di spessore di Breslow> 1mm che è stato asportato radicalmente 3 mesi prima della randomizzazione. Margini di escissione di almeno 1 cm sono necessari. Nelle zone di testa e del collo e in caso di posizioni sulla estremità distale ristretti margini accettabili purché sono radicali.
-In caso subjeccts sono stati sottoposti a gestione temporanea del nodo sentinella dopo l'escissione del primario, questo deve essere fatto entro il termine di 3 mesi tra la data di escissione finale del primario e la data di randomizzazione.
-I soggetti devono avere un performance status ECOG di 0 o 1.
-Soggetti deve essere compreso tra 18-70 anni di età.
-Soggetti devono avere un'adeguata epatica, renale e la funzione del midollo osseo come definito dai seguenti parametri ottenuti entro 4 settimane prima dell'inizio del trattamento in studio.
-Soggetti devono dare il consenso informato secondo ICH-GCP o nazionale / politica locale. |
|
E.4 | Principal exclusion criteria |
-Subjects suffering form a mucous membrane melanoma or ocular melanoma
-Subjects who have evidence of (non-)regional lymph node metastases or intransit metastases (even if they have been resected)
-Subjects whose disease cannot be completely surgically resected
-Subjects who have not recovered from the effects of recent surgery
-Subjects with a history of prior malignancy within the past 10 years other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ
-Subjects who have severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease
-Subjects with thyroid dysfunction not responsive to therapy
-Subjects with uncontrolled diabetes mellitus
-Subjects suffering from an active autoimmune disease
-Subjects with active and/or uncontrolled infection, including active hepatitis
-Subjects who have a histroy of seropositivity for HIV
-Subjects who hqve a history of neuropsychiatric disorder requiring hospitalization
-Subjects who are known to be actively abusing alcohol or drugs
-Subjects who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception
-Subjects with a medical condition requiring chronic systemic corticosteroids
-Subjects who have received any experimental therapy within 30 days prior to randomization in this study
-Subjects who have received any prior chemotherapy, immunotherapy, hormonal or radiation therapy for melanoma
-Subjects who have previously received interferon-alpha for any reason
-Subjects hqving history of epilepsy or other major central nervos system disease
-Subjects having eyes disorders |
-Soggetti affetti formare un melanoma delle mucose o melanoma oculare
-Soggetti che hanno evidenza di (non) metastasi nei linfonodi regionali o metastasi InTransit (anche se sono stati sottoposti a resezione)
-I soggetti con malattia non può essere completamente asportato chirurgicamente
-I soggetti che non hanno recuperato dagli effetti del recente intervento chirurgico
-Soggetti con anamnesi di neoplasia maligna prima negli ultimi 10 anni oltre chirurgicamente guarito non-melanoma, cancro della pelle o carcinoma cervicale in situ
-Soggetti che hanno gravi malattie cardiovascolari, aritmie, cioè che richiedono un trattamento cronico, insufficienza cardiaca congestizia (classe NYHA III o IV) o cardiopatia ischemica sintomatica
-I soggetti con disfunzione tiroidea non responsive alla terapia
-I soggetti con diabete mellito non controllato
-Soggetti affetti da una malattia autoimmune attiva
-I soggetti con infezione attiva e / o non controllata, tra cui epatite attiva
-Soggetti che hanno un Histroy di sieropositività per l'HIV
-Soggetti che hqve una storia di disturbi neuropsichiatrici che richiedono ospedalizzazione
-Soggetti che sono noti per essere attivamente abusando di alcol o droghe
-I soggetti che sono in stato di gravidanza, allattamento, o di potenziale riproduttivo e non praticare un mezzo efficace di contraccezione
-Soggetti affetti da patologie croniche che richiedono corticosteroidi sistemici
-Soggetti che hanno ricevuto una terapia sperimentale nei 30 giorni precedenti la randomizzazione in questo studio
-Soggetti che hanno ricevuto alcun precedente chemioterapia, immunoterapia, ormonale o radioterapia per il melanoma
-Soggetti che hanno precedentemente ricevuto l'interferone-alfa, per qualsiasi motivo
Di soggetti con storia di epilessia o hqving altro grande centrale del sistema nervos malattia
-Soggetti con disturbi agli occhi |
|
E.5 End points |
E.5.1 | Primary end point(s) |
-Relapse free survival (RFS) |
-La sopravvivenza libera da recidiva (RFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 years and 3 months |
6 anni e 3 mesi |
|
E.5.2 | Secondary end point(s) |
-Distant metastasis free survival (DMFS)
-Overal survival (OS)
-Toxicity
-Quality of life |
-A distanza sopravvivenza libera da metastasi (DMF)
-Overal sopravvivenza (OS)
-Tossicità
-Qualità della vita |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Distant metastasis free survival (DMFS):8 years
-Overal survival (OS):8 years
-Toxicity:during all the conduct of the trial
-Quality of life:6 years and 3 months |
-A distanza sopravvivenza libera da metastasi (DMF): 8 anni
-Overal sopravvivenza (OS): 8 anni
-Tossicità: durante tutto lo svolgimento del processo
-Qualità della vita: 6 anni e 3 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 | 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) | 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 | 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 |
|
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 | 6 |
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 | 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
|
End of study occurs when all of the following criteria have been satisfied: 1.Thirty days after all patients have stopped protocol treatment 2.The trial is mature (i.e. reached the required number of events) for each of the two final analyses of the endpoints (RFS and OS) as defined in the protocol. 3.The database has been fully cleaned and frozen for each of these 2 final analyses. |
Trenta giorni dopo che tutti i pazienti ha interrotto la terapia del protocollo Il processo è maturo per ciascuna delle due analisi finali degli endpoint Il database è stato completamente pulita e congelati per ciascuna di queste due analisi final |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
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 | 9 |
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 |