E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Soft Tissue Sarcoma |
sarcoma dei tessuti molli di stadio avanzato o metastatico |
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E.1.1.1 | Medical condition in easily understood language |
cancer of the connective tissue that has worsened or grown in other parts of the body |
carcinoma del tessuto connettivo che ¿ progredito o ha metastatizzato in altri distretti corporei |
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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 | HLT |
E.1.2 | Classification code | 10041298 |
E.1.2 | Term | Soft tissue sarcomas histology unspecified |
E.1.2 | System Organ Class | 100000004864 |
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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 |
The primary objective is to compare doxorubicin plus olaratumab versus doxorubicin plus placebo with respect to OS in 2 populations: (1) Patients with advanced or metastatic soft tissue sarcoma (STS) not amenable to treatment with surgery or radiotherapy with curative intent (2) Patients with advanced or metastatic leiomyosarcoma (LMS) not amenable to treatment with surgery or radiotherapy with curative intent |
L¿obiettivo primario ¿ confrontare doxorubicina pi¿ olaratumab vs. doxorubicina pi¿ placebo in termini di OS in 2 popolazioni: (1) Pazienti con sarcoma dei tessuti molli in stadio avanzato o metastatico non trattabile mediante chirurgia o radioterapia con intento curativo (2) Pazienti con leiomiosarcoma in stadio avanzato o metastatico non trattabile mediante chirurgia o radioterapia con intento curativo
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare doxorubicin plus olaratumab versus doxorubicin plus placebo with respect to: ¿ Progression-free survival (PFS) ¿ Objective response rate (ORR) (complete response [CR] + partial response [PR]) ¿ Disease control rate (DCR; CR + PR + stable disease [SD]) ¿ Patient-reported outcomes (PROs): Pain, Health-related Quality of Life (HRQoL), and health status ¿ Duration of response (DoR) ¿ Duration of disease control (DDC) ¿ Safety and tolerability ¿ Pharmacokinetics (PK) and immunogenicity |
Gli obiettivi secondari dello studio riguardano il confronto di doxorubicina pi¿ olaratumab vs. doxorubicina pi¿ placebo in termini di: ¿ Sopravvivenza libera da progressione (PFS) ¿ Tasso di risposta obiettiva (ORR) (risposta completa [CR] + risposta parziale [PR]) ¿ Tasso di controllo della malattia (DCR: CR + PR + malattia stabile [SD]) ¿ Outcome riferiti dal paziente (PRO): dolore, qualit¿ di vita correlata alla salute (HRQoL) e stato di salute ¿ Durata della risposta (DoR) ¿ Durata del controllo di malattia (DDC) ¿ Sicurezza e tollerabilit¿ ¿ Farmacocinetica (PK) e immunogenicit¿
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
18 years or older at study entry Histologically confirmed diagnosis of locally advanced unresectable or metastatic STS not amenable to curative treatment with surgery or radiotherapy. Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. (excludes GIST & Kaposi). Note: Evidence of disease progression isrequired for patients that are not newly diagnosed. Measurable or nonmeasurable but evaluable disease by RECIST 1.1 ECOG 0-1 May have had any number of prior systemic therapies for advanced/metastatic disease, however may not have received any previous treatment with anthracyclines. All previous anticancer treatments must be completed = 3 weeks (21 days) prior to first dose of study drug. Consent to provide archived FFPE tumor tissue or be subject to a pretreatment re-biopsy of primary or metastatic tumor tissue future central pathology review and translational research (if archived tissue is unavailable) LVEF ›= 50% Life expectancy, in opinion of the investigator, is at least 3 months Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to randomization. |
Età pari o superiore a 18 anni al momento dell’ingresso nello studio Diagnosi confermata istologicamente di sarcoma dei tessuti molli localmente avanzato non resecabile o metastatico, non trattabile mediante chirurgia o radioterapia curativa. I soggetti con liposarcoma di grado 1 sono considerati eleggibili in presenza di evidenza istologica o radiografica di evoluzione verso una forma più aggressiva. (con l’esclusione di GIST e Kaposi) Nota: L'evidenza di progressione di malattia è richiesta ai pazienti che non hanno ricevuto diagnosi di recente. Malattia misurabile o non misurabile ma valutabile sulla base dei criteri RECIST 1.1 ECOG 0-1 È ammesso qualsiasi numero di terapie sistemiche pregresse per malattia avanzata/metastatica, ma il soggetto non deve essere stato sottoposto a trattamento pregresso con antracicline. Tutte le terapie anticancro pregresse devono essere state completate da = 3 settimane (21 giorni) prima della prima dose di farmaco dello studio. Consenso a fornire un campione d’archivio di tessuto tumorale fissato in formalina e incluso in paraffina o a sottoporsi a un nuovo prelievo bioptico di tessuto dal tumore primitivo o metastatico prima del trattamento per una successiva revisione patologica centralizzata e attività di ricerca traslazionale (qualora non sia disponibile un campione tissutale d’archivio) LVEF ›=50% La speranza di vita, a giudizio dello sperimentatore, è di almeno 3 mesi Le donne potenzialmente fertili devono sottoporsi a un test di gravidanza su siero entro 7 giorni prima della randomizzazione e ottenere esito negativo.
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E.4 | Principal exclusion criteria |
Diagnosed with GIST or Kaposi sarcoma Active CNS or brain metastasis at randomization The patient has received prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones; the patient has received treatment with olaratumab or has participated in a prior olaratumab trial. Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation Electively planned or required major surgery during the study Uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics, symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF<50%), severe myocardial insufficiency, cardiac arrhythmia, cardiomyopathy, or a psychiatric illness/social situation that would limit compliance with study requirements Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction QTc interval › 450 msec and › 470 msec for males and females, respectively, on screening ECG Pregnant or breastfeeding Known active fungal, bacterial, or viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required) |
Diagnosi di GIST o sarcoma di Kaposi Metastasi del SNC o cerebrali attive alla randomizzazione Il paziente ha esperienza di trattamento pregresso con doxorubicina, epirubicina, idarubicina e/o altre antracicline e antracenedioni; il paziente ha esperienza di trattamento pregresso con olaratumab o ha preso parte ad un precedente studio clinico con Olaratumab. Radioterapia pregressa dell’area mediastinica/pericardica o irraggiamento dell’intera pelvi Intervento chirurgico maggiore necessario o programmato in regime di elezione nel corso dello studio Malattia intercorrente non controllata inclusa, tra le altre, un’infezione in corso/attiva con necessità di terapia antibiotica per via parenterale, insufficienza cardiaca congestizia sintomatica, disfunzione del ventricolo sinistro (LVEF <50%), grave insufficienza miocardica, aritmia cardiaca, cardiomiopatia, o malattia psichiatrica/situazione sociale che limiterebbe la compliance ai requisiti previsti dallo studio Angina pectoris instabile, angioplastica, stent cardiaco o infarto del miocardio Intervallo QTc ›450 ms e ›470 ms rispettivamente per i soggetti di sesso maschile e femminile all’ECG di screening Donna incinta o in allattamento Infezione micotica nota, batterica o virale nota, incluse le infezioni da virus dell’immunodeficienza umana (HIV) o da virus dell’epatite (A, B o C) (screening non richiesto)
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall suvival |
Sopravvivenza globale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
time from randomization to death |
Tempo intercorrente tra la randomizzazione e il decesso |
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E.5.2 | Secondary end point(s) |
¿ PFS ¿ ORR ¿ DCR ¿ Time to first worsening of the mBPI-sf (Brief Pain Inventory Short Form Modified) "worst pain" score ¿ Duration of response ¿ Duration of disease control ¿ Safety and tolerability ¿ Pharmacokinetics (PK) and immunogenicity
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¿ PFS ¿ ORR ¿ DCR ¿ Tempo al primo peggioramento del punteggio mBPI-sf (Brief Pain Inventory Short Form Modified) di ¿dolore peggiore¿ ¿ Durata della risposta ¿ Durata del controllo di malattia ¿ Sicurezza e tollerabilit¿ ¿ Farmacocinetica (PK) e immunogenicit¿
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS is determined from the date of randomization and the date on which disease progresses or the date on which the patient dies, from any cause, whichever is earlier. Response rates (ORR=CR+PR/Randomized subjects) (DCR=CR+PR+SD/Randomized subjects) will be based on evaluations done every 6 weeks until radiographic documentation of progression. PRO: Day 1 of every cycle, Short-Term Follow-Up and Long-Term Follow- Up DoR and duration of disease control is measured from the time measurement criteria are first met for CR or PR until the first date of objective progression is observed . Safety and tolerability: On study treatment, Short-Term Follow-Up and Long-Term Follow-Up PK and immunogenicity: At various time points according to the protocol and in the event of IRR |
La PFS ¿ intesa come l¿intervallo di tempo intercorrente tra la data di randomizzazione e la data in cui la malattia progredisce o il paziente muore per qualsiasi causa (a seconda di quale evento si verifichi per primo). I tassi di risposta (ORR=CR+PR/soggetti randomizzati) (DCR=CR+PR+SD/soggetti randomizzati) si baseranno su valutazioni condotte ogni 6 settimane fino a documentazione radiografica di progressione della malattia. PRO: giorno 1 di ogni ciclo, follow-up a breve termine e follow-up a lungo termine La DoR e la durata del controllo di malattia sono intese come l¿intervallo di tempo intercorrente tra il primo momento in cui i criteri di misurazione per CR o PR vengono soddisfatti e la prima osservazione di progressione obiettiva della malattia. Sicurezza e tollerabilit¿: durante |
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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 | 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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Denmark |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |