E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma |
Leiomiosarcoma e liposarcoma ben differenziato/dedifferenziato del retroperitoneo in fase avanzata |
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E.1.1.1 | Medical condition in easily understood language |
Tumours of muscle tissue (leiomyosarcoma) and tumours of fat tissue |
Tumori del tessuto muscolare (leiomiosarcoma) e tumori del tessuto grasso (liposarcoma) |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10024627 |
E.1.2 | Term | Liposarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073135 |
E.1.2 | Term | Dedifferentiated liposarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10024189 |
E.1.2 | Term | Leiomyosarcoma |
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 |
Confirming the activity of the drug trabectedin as second/further line treatment in retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma expressed in terms of slowing down tumour growth.
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Confermare l’attività della trabectedina come seconda/ulteriore linea di trattamento nei leiomiosarcomi e nei liposarcomi ben differenziati/dedifferenziati del retroperitoneo. |
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E.2.2 | Secondary objectives of the trial |
To investigate the peculiar benefit provided by trabectedin in typical retroperitoneal sarcomas, in order to help multidisciplinary clinical decision-making |
Un altro obiettivo di questo studio è quello di valutare il beneficio fornito dalla trabectedina nei sarcomi retroperitoneali, in modo da supportare il processo decisionale multidisciplinare nella gestione dei sarcomi in questa sede |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
"A Phase II study on Trabectedin in advanced retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma - biologic sub-study"
Version 1.2, 14/04/2013
Translational studies will be performed, with the aim of characterising the tumour biological features associated with different response patterns to trabectedin by miR determination in both neoplastic and plasma tissue in patients who will undergo surgery after trabectedin, comparing tumour tissue specimens collected before and after treatment |
Saranno effettuati studi a latere con lo scopo di definire le caratteristiche biologiche tumorali associate a differenti tipologie di risposta a trabectedina. Queste valutazioni saranno eseguite in tutti i Pazienti che si sottoporranno a chirurgia dopo il trattamento con trabectedina, attraverso l’analisi comparata di campioni di tessuto tumorale raccolti prima e dopo il trattamento con trabectedina |
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E.3 | Principal inclusion criteria |
- Persistent or locally relapsed and/or metastatic disease (in case of local disease, surgery may be technically feasible or not, but the clinical judgment must be that medical therapy is indicated) - Pathology specimens available for centralized review - Age ≥ 18 years - ECOG PS ≤ 2 - One or more previous systemic treatments employing anthracyclines and ifosfamide (unless one or both are clinically contraindicated) - Measurable disease, as defined by RECIST criteria - A minimum of 3 weeks since any previous medical therapy - Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower - Adequate haematological, renal and liver functions - Ability and willingness to provide informed consent
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- Persistenza di malattia o recidiva locale e/o malattia metastatica (in caso di malattia localizzata, la chirurgia può essere tecnicamente indicata o meno, ma il giudizio clinico deve indicare la necessità di una terapia medica) - Campioni di anatomia patologica disponibili per la revisione centralizzata - Età ≥ di 18 anni - ECOG PS ≤ 2 - Uno o più trattamenti sistemici precedenti con antraciclina e ifosfamide (a meno che uno o entrambi non siano clinicamente controindicati) - Malattia misurabile, secondo i criteri RECIST - Un intervallo minimo di 3 settimane da qualsiasi terapia medica precedente - Assenza di eventi avversi in corso superiori al grado 1 (secondo il NCI CTC) provocati da trattamenti precedenti - Adeguata funzionalità ematica, renale ed epatica - Consenso informato firmato
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E.4 | Principal exclusion criteria |
- Pregnant or breast-feeding women - Prior exposure to trabectedin - Peripheral neuropathy, Grade 2 or higher - History of other malignancies (except for basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission for 5 years or more and judged of negligible potential of relapse - Known central nervous system (CNS) metastases - Active viral hepatitis or chronic liver disease - Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias - Active major infection - Other serious concomitant illnesses
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- Donne in gravidanza o che allattano al seno - Precedente trattamento con trabectedina - Neuropatia periferica di Grado 2 o maggiore - Anamnesi di altre neoplasie (ad eccezione del basalioma o del carcinoma in situ della cervice, adeguatamente trattati), a meno che non siano in remissione da 5 anni o più e giudicate con scarso potenziale di recidiva - Metastasi a carico del sistema nervoso centrale - Epatite virale attiva o epatite cronica - Funzionalità cardiaca instabile, inclusa insufficienza cardiaca congestizia o angina pectoris, infarto miocardico avvenuto entro un anno dall’arruolamento nello studio, ipertensione arteriosa non controllata o aritmia - Gravi infezioni in atto - Altre patologie serie concomitanti
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of responders to trabectedin by means of Growth Modulation Rate, that is the ratio between PFS under trabectedin (PFS) and time to progression after previous chemotherapy treatment (TTP1). The primary end point will be calculated in the overall sample |
Proporzione delle risposte definite attraverso il Growth Modulation Rate, ovvero il rapporto tra la progressione libera da malattia (PFS) dopo trattamento con trabectedina e il tempo alla progressione (TTP1) dopo la prima/precedente linea di trattamento in ogni singolo Paziente |
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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) |
- Objective response (OR) in the overall sample - Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment - PFS and OR in the two eligible histological types - PFS in patients who undergo surgery after, or during, trabectedin treatment and those who do not - Safety profile - Efficacy of trabectedin in reducing cancer related pain |
- Risposta oggettiva (OR) nell’intero campione. - Risposta patologica del tumore nelle due tipologie istologiche eligibili, in Pazienti che sono sottoposti a chirurgia dopo il trattamento - PFS e OR nelle due tipologie istologiche eligibili - PFS in Pazienti che sono sottoposti a chirurgia dopo o durante la terapia medica e in quelli che non sono sottoposti a chirurgia - Profilo di sicurezza della trabectedina - Efficacia della trabectedina nel ridurre il dolore associato a tumore
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 21 |
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 | 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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LVLS |
Ultima visita ultimo soggetto arruolato (LVLS) |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |