E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with myxoid/round cell liposarcoma treated with at least 4 cycle of T alone with a stable disease at the last tumor evaluation |
Pazienti con diagnosi di liposarcoma mixoide/a cellule rotonde trattati per almeno 4 cicli con trabectedina da sola e con malattia stabile in base all’ultima valutazione di malattia. |
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E.1.1.1 | Medical condition in easily understood language |
Patients who have been diagnosed with round cell myxoid liposarcoma and who have been treated with only trabectedin and who according to the latest assessment have stable disease. |
Pazienti con diagnosi di liposarcoma di tipo mixoide/ a cellule rotonde che sono stati trattati negli ultimi 4 cicli con solo il farmaco trabectedina e con malattia stabile all'ultima valutazione. |
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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 | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10028395 |
E.1.2 | Term | Musculoskeletal and connective tissue disorders |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10024628 |
E.1.2 | Term | Liposarcomas malignant |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073139 |
E.1.2 | Term | Round cell 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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10073137 |
E.1.2 | Term | Myxoid liposarcoma |
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 |
This study is aimed at assessing the activity of T in combination with P in patients diagnosed with round cell myxoid liposarcomas or dedifferentiated G1 and G2 liposarcomas with stable disease after 4 cycles of treatment with T administered in monotherapy. |
Lo studio è finalizzato a valutare l'attività di Trabectedina (T) in combinazione con Pioglitazione (P) in pazienti con diagnosi di liposarcoma mixoide a cellule rotonde o liposarcomi dedifferenziati G1 e G2 con malattia stabile (SD) dopo almeno 4 cicli di trattamento con T somministrata in monoterapia. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be to describe the efficacy and the safety of the combination treatment with T and P. |
Descrivere l'efficacia e la sicurezza di trabectedina in combinazione con pioglitazone |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of myxoid/round cell liposarcomas 2. Histological diagnosis confirmation by a reference centre 3. Age = 18 years 4. ECOG PS =2 5. One or more previous systemic treatments employing anthracyclines +/- ifosfamide (unless one or both are clinically contraindicated) 6. Four or more previous cycles of T with a stable disease as defined by RECIST criteria 7. Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or higher 8. Provision of signed informed consent |
1. Diagnosi di liposarcoma mixoide/a cellule rotonde 2. Diagnosi di malattia confermata da un centro di riferimento per il trattamento dei sarcomi 3. Età pari o superiore a 18 anni 4. ECOG Performance Status inferiore o pari a 2 5. Almeno un trattamento sistemico precedente a base di antracicline +/- ifosfamide (a meno che uno o entrambi non siano clinicamente controindicati) 6. Stabilità di malattia (SD) dopo almeno quattro cicli precedenti di terapia sistemica a base di T , in accordo ai criteri RECIST 1.1 7. Risoluzione di eventuali eventi avversi correlati a terapie precedenti di grado 1 o superiore secondo la classificazione NCI CTC 8. Consenso informato scritto |
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E.4 | Principal exclusion criteria |
1. Pregnant or breast-feeding women 2. Partial response or progression disease as per RECIST criteria to the previous treatment with T 3. Inadequate haematological, renal and liver functions 4. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse 5. Known central nervous system (CNS) metastases 6. Active viral hepatitis or chronic liver disease 7. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias 8. Active major infection |
1. Donne in stato di gravidanza o allattamento 2. Risposta parziale o malattia in progressione al trattamento precedente con T secondo i criteri RECIST 3. Funzionalità ematologica, renale o epatica inadeguate 4. Storia di altre neoplasie maligne (ad eccezione del carcinoma basocellulare o del cancro cervicale in situ, adeguatamente trattati), a meno che in remissione da almeno 5 anni o giudicate come recidive potenzialmente trascurabili 5. Presenza di metastasi note a carico del sistema nervoso centrale (SNC) 6. Epatite virale attiva o malattia epatica cronica 7. Condizione cardiaca instabile, tra cui insufficienza cardiaca congestizia o angina pectoris, infarto del miocardio, entro un anno prima dell’arruolamento, ipertensione arteriosa incontrollata o aritmie 8. Grave infezione attiva |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response (OR) according to RECIST criteria or CHOI criteria |
Risposta oggettiva (OR) in accordo ai criteri RECIST o CHOI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The objective response (CR or PR) according to RECIST v. 1.1 or CHOI criteria will be evaluated during the treatment until disease progression, consent withdrawal, lost to follow-up, death. |
La risposta oggettiva (CR o PR), sarà valutata durante il trattamento in accordo ai criteri CHOI e RECIST v. 1.1 fino a progressione, ritiro del consenso, perdita al follow-up, morte. |
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E.5.2 | Secondary end point(s) |
1. Number and severity of Adverse Events according to NCI CTC v.5.0 2. Pharmacokinetics parameters |
1. Numero e severità di eventi avversi in accordo con NCI CTC v.5.0 2. Parametri di farmacocinetica |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The detection time will be calculated for the patients who will not experience serious adverse events and who maintain stable pharmacokinetic parameters during the study. |
Il tempo di rilevazione verrà calcolato in tutti i pazienti che non sperimenteranno gravi eventi avversi e che mantengano i parametri di farmacocinetica stabili durante l'intero studio. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Studio pilota monocentrico e a braccio singolo |
Single institution, single arm, pilot study |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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
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If no response, about the 10 patients enrolled in the study, will be observed, the study will be stopped, on the contrary when the first enrolled patient is observed in response and after at least 4 patients evaluated with pharmacokinetic parameters, the pilot phase of the study will be interrupted and the second randomized phase can begin. |
se non si osserverà alcun paziente in risposta, sui 10 pazienti arruolati, lo studio verrà interrotto al contrario quando sarà osservato il primo paziente in risposta e dopo almeno 4 pazienti con parametri farmacocinetici valutati, la fase pilota dello studio verrà interrotta e potrà iniziare la seconda fase randomizzata. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |