E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High malignancy grade of osteosarcoma relapse |
recidiva di osteosarcoma ad alto grado di malignità |
|
E.1.1.1 | Medical condition in easily understood language |
relapsed osteosarcoma |
Ricaduta in pazienti affetti da osteosarcoma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031296 |
E.1.2 | Term | Osteosarcoma recurrent |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy and tollerability of two chemotherapeutic regimens (either Cyclophosphamide+ Etoposide or high dose Ifosfamide) currently used to treat relapsed Osteosarcoma patients |
confrontare l’efficacia/tollerabilità di due regimi chemioterapici (Ciclofosfamide ed Etoposide o Ifosfamide ad alte dosi) attualmente utilizzati nel trattamento delle recidive di Osteosarcoma |
|
E.2.2 | Secondary objectives of the trial |
To evaluate Clinical Benefit, Toxicity, Quality of life, Overall Survival, Progression Free Survival |
Valutare: Beneficio clinico,Tossicità,Qualità della vita,Overall Survival,Progression Free Survival |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.patients with high-grade malignant relapsed osteosarcoma 2.age at diagnosis <50 years 3.Lansky score o Karnofsky Performance status > 60% 4.First or subsequent relapse of osteosarcoma surgically unresectable or for whom surgery was oncologically not appropriate 5.Good organ function defined by: 1) serum creatinine < 2 times the upper limit for age, 2) total bilirubin <1.5 times the upper limit of age, 3) transaminases ≤ 2.5 times the upper limit for age, 4) alkaline phosphatase ≤ 5 times the upper limit for age (with the exclusion of patients with skeletal metastases) 6.Normal Heart function (VEF > 50%) 7.White blood cells >3 x 109/l and platelets >100 x 109/l 8.For female patients with childbearing potential, a negative test for pregnancy is to be considered before entry on study 9.Written signed informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations |
1.Diagnosi iniziale di recidiva di osteosarcoma ad alto grado di malignità 2.Età alla diagnosi di recidiva di osteosarcoma <50 anni 3.Lansky score o Karnofsky Performance status > 60% 4.Malattia in prima o ulteriore recidiva non resecabile chirurgicamente o per i quali l’intervento chirurgico viene giudicato oncologicamente non adeguato. 5.Buona funzionalità epatica e renale definita dai seguenti parametri: 1) creatinina serica < 2 volte il limite superiore per età; 2) bilirubina totale < 1.5 volte il limite superiore per età; 3) transaminasi ≤ 2.5 volte il limite superiore per età; 4) fosfatasi alcalina < 5 volte il limite superiore per età (con l’esclusione dei pazienti con metastasi scheletriche). 6.Frazione di eiezione ventricolare > 50%. 7.Globuli bianchi >3 x 109/l e piastrine >100 x 109/l. 8.I soggetti di sesso femminile che abbiano già avuto menarca, devono presentare un test di gravidanza negativo prima dell’inizio dello studio. 9.Sottoscrizione del modulo di consenso alla partecipazione allo studio da parte del soggetto interessato o da chi ne esercita la patria potestà. |
|
E.4 | Principal exclusion criteria |
1.Medical contraindications to the use of the drugs included in the Protocol. 2.Psychological conditions that don’t ensure either a good adhesion to the Protocol or a proper management of toxicity or a proper understanding of the study 3.Either HBV or HCV or HIV active infection 4.Previouly treatment with either Cyclophosphamide+ Etoposide or high dose Ifosfamide Pregnant or lactating patients |
1.Controindicazioni mediche all'uso dei farmaci previsti dal Protocollo. 2.Condizioni mentali o sociali che non garantiscano una adeguata adesione al protocollo, una corretta gestione domiciliare della tossicità, una adeguata comprensione della partecipazione allo studio. 3.Infezione da HBV, HCV e HIV in fase attiva. 4.Precedente trattamento con Ciclofosfamide-Etoposide oppure con Ifosfamide ad alte dosi. 5.Gravidanza o allattamento in atto al momento della diagnosi di recidiva. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the Overall Response Rate (ORR) defined as the percentage of patients with complete or partial response |
Determinare la Overall Response Rate (ORR), cioè la percentuale di pazienti che presentano una risposta completa o parziale |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 2 chemotherapy cycles |
dopo il 2° ciclo di chemioterapia |
|
E.5.2 | Secondary end point(s) |
Evaluate: Number of patients with complete response or stable disease >=4 months Number of patients with toxicity grade ≥3 (NCI CTAE version 4.0) Number of patients with death for any cause since the date of randomization to the date of last available follow-up Number of patients with relapse/progression/death for any cause since the date of randomization to the date of last available follow-up Quality of life evaluation by PedsQLTM and EORTC QLQ-C30 criteria |
Determinare:
Proporzione di pazienti che presentano risposta completa o stabilizzazione di malattia per ≥ 4 mesi,
Proporzione di pazienti che sviluppano tossicità di grado ≥3 secondo i criteri CTCAE versione 4.0 , Proporzione di pazienti che giungono al decesso per qualsiasi causa dalla data della randomizzazione alla data dell’ultimo follow-up disponibile, Proporzione di pazienti che presentano recidiva/progressione/decesso per qualsiasi causa dalla data della randomizzazione alla data dell’ultimo follow up disponibile, Valutazione della qualità della vita misurata con i criteri PedsQLTM (pz pediatrici) e EORTC QLQ-C30 (pz adulti) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After each cycle for toxicity,after 2 month for response and within 5 years for follow-up evaluations |
La tossicità viene rilevata ad ogni ciclo, la risposta viene valuata dopo 2 mesi, gli altri endpoints vengono valuati entro i 5 anni di follow-up |
|
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) | 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) | Yes |
E.8.2.2 | Placebo | No |
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 | 19 |
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
|
5 years after the last completed treatment |
5 anni dal completamento della terapia dell'ultimo paziente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |