E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Synovial Sarcoma |
Sarcoma Sinoviale |
|
E.1.1.1 | Medical condition in easily understood language |
Synovial Sarcoma |
Sarcoma Sinoviale |
|
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 | PT |
E.1.2 | Classification code | 10042863 |
E.1.2 | Term | Synovial sarcoma |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of ramucirumab in combination with gemcitabine and docetaxel compared with gemcitabine and docetaxel in pediatric and young adult patients with SS (SS = synovial sarcoma). |
Valutare l’efficacia di ramucirumab in associazione a gemcitabina e docetaxel rispetto a gemcitabina e docetaxel in pazienti pediatrici e giovani adulti affetti da SS (SS = sarcoma sinoviale) |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of ramucirumab in combination with gemcitabine and docetaxel compared with gemcitabine and docetaxel in pediatric and young adult patients with SS. - To characterize the PK of ramucirumab when co-administered with gemcitabine and docetaxel in pediatric and young adult patients with SS. - To assess the immunogenicity of ramucirumab when co-administered with gemcitabine and docetaxel in pediatric and young adult patients with SS. |
- Valutare la sicurezza e la tollerabilità di ramucirumab in associazione a gemcitabina e docetaxel rispetto a gemcitabina e docetaxel in pazienti pediatrici e giovani adulti affetti da SS - Caratterizzare la PK di ramucirumab quando è somministrato in concomitanza con gemcitabina e docetaxel in pazienti pediatrici e giovani adulti affetti da SS - Valutare l’immunogenicità di ramucirumab quando è somministrato in concomitanza con gemcitabina e docetaxel in pazienti pediatrici e giovani adulti affetti da SS |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with either relapsed, recurrent, or refractory SS. - Patients must be >11 kg at the time of study enrollment. - The patient has a Lansky (<16 years of age; Lansky et al. 1987) or Karnofsky (=16 years of age; Karnofsky et al. 1948) performance score of at least 50. - Patients must be 36 months to =29 years of age at the time of study enrolment. - Patients must •have measurable disease by RECIST 1.1 •have received at least one prior line of systemic treatment (including neoadjuvant and adjuvant chemotherapy) that contains ifosfamide and/or doxorubicin, and any approved therapies for which they are eligible, unless the patient is not a suitable candidate for the approved therapy. •not be eligible for surgical resection at time of enrollment - Patients must not have received prior exposure to ramucirumab. - Patient with adequate laboratory values and hematologic, coagulation, liver, cardiac, renal and bladder function, and adequate blood pressure (BP) control as per protocol. |
- I pazienti deve avere un SS recidivante o ricorrente o refrattaria -I pazienti devono avere un peso corporeo > 11 kg al momento dell'arruolamento nello studio - Il paziente ha un punteggio di performance di Lansky (<16 anni; Lansky et al. 1987) o Karnofsky (=16 anni; Karnofsky et al. 1948) di almeno 50. - I pazienti devono avere un'età compresa tra 36 mesi e =29 anni al momento dell'arruolamento nello studio. - I pazienti devono • avere una malattia misurabile secondo RECIST 1.1 • avere ricevuto almeno una precedente linea di trattamento sistemico (inclusa la chemioterapia neoadiuvante e adiuvante) contenente ifosfamide e / o doxorubicina e qualsiasi terapia approvata per la quale sono ammissibile, a meno che il paziente non sia un candidato idoneo per la terapia approvata • non essere idoneo per la resezione chirurgica al momento dell'iscrizione - I pazienti non devono aver ricevuto una precedente esposizione a ramucirumab. - Paziente con adeguati valori di laboratorio ed ematologici, coagulazione, funzionalità epatica, cardiaca, renale e vescicale e controllo adeguato della pressione sanguigna (BP) come da protocollo. |
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E.4 | Principal exclusion criteria |
- Patients who have had allogeneic bone marrow or solid organ transplant are excluded. - Patients who have active infections requiring therapy. - Patients who have a history of fistula, gastrointestinal (GI) ulcer or perforation, or intra-abdominal abscess within 3 months of study enrolment are not eligible. - Patients with a bowel obstruction, extensive intestinal resection or history or presence of inflammatory enteropathy or other GI pathology as per protocol. - Patients with a history of hepatorenal syndrome. -Patients with a known hypersensitivity to ramucirumab , gemcitabine, docetaxel or agents formulated with Polysorbate 80 - Patients with evidence of active bleeding or a history of significant (= Grade 3) bleeding event, deep vein thrombosis requiring medical intervention (including pulmonary embolism), hemoptysis or other signs of pulmonary haemorrhage, or esophageal varices within 3 months of enrollment are not eligible. - Patients with a bleeding diathesis or vasculitis are not eligible. - Patients with a history of central nervous system (CNS) arterial/venous thromboembolic events (VTEs) including transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months of study enrolment are not eligible. - Patients with myocardial infarction or unstable angina within the prior 6 months. - Patients with significant vascular disease or peripheral vascular disease. - Patients with a history of hypertensive crisis or hypertensive encephalopathy within 6 months of study enrolment are not eligible. - Patients who have non-healing wound, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrolment are not eligible. - Patients previously treated and progressed on combination gemcitabine or docetaxel. (Patients who received combination as maintenance therapy, without progression, would be eligible.) - Patients with a known hypersensitivity to gemcitabine, docetaxel or agents formulated with Polysorbate 80. - Patients who have previously received any exposure to ramucirumab are not eligible. - Patients with clinical or radiologic findings consistent with interstitial pneumonia or pulmonary fibrosis. - Patients with CNS involvement are ineligible |
Sono esclusi dallo studio:
- Pazienti che hanno eseguito un trapianto allogenico di midollo spinale o di organi solidi - Pazienti con infezioni attive che necessitano un trattamento - Pazienti con anamnesi di fistole, ulcera o perforazione gastrointestinale (GI), o di ascesso intra-addominale nei 3 mesi precedenti all'arruolamento nello studio - Pazienti con ostruzione intestinale, resezione intestinale estensiva o anamnesi o presenza di enteropatia infiammatoria o di un'altra patologia GI, come specificato nel Protocollo - Pazienti con una storia di sindrome epatorenale - Pazienti con ipersensibilità nota a ramucirumab , gemcitabina, docetaxel o a farmaci contenenti Polysorbate 80 nella formulazione - Pazienti con evidenza di sanguinamento attivo o storia di eventi clinicamente significativi (Grado 3) di sanguinamento, trombosi venosa profonda che richiede un intervento medico (inclusa l'embolia polmonare), emottisi o altri segni di emorragia polmonare, o varici esofagee nei 3 mesi precedenti all’arruolamento - Pazienti con diatesi emorragica o vasculite - Pazienti con anamnesi di tromboembolismo arteriosio/venoso (VTE) a carico del sistema nervoso centrale (SNC), incluso l’attacco ischemico transitorio (TIA) o l’incidente cerebrovascolare (CVA) nei 6 mesi precedenti all’arruolamento - Pazienti con infarto miocardico o angina instabile nei 6 mesi precedenti all’arruolamento - Pazienti con patologia vascolare o vascolare periferica clinicamente significativa - Pazienti con storia di crisi ipertensiva o encefalopatia ipertensiva nei 6 mesi precedenti all’arruolamento - Pazienti con ferite non rimarginabili, fratture ossee non risaldate o incompletamente risaldate, o con fratture ossee esposte (aperte) al momento dell’arruolamento - Pazienti precedentemente trattati con gemcitabina o docetaxel, che hanno manifestato progressione della malattia (I pazienti che hanno assunto la terapia combinata come terapia di mantenimento, senza progressione, sono idonei all’arruolamento) - Pazienti con ipersensibilità nota a gemcitabina, docetaxel o a farmaci formulati con Polisorbato 80 - Pazienti che hanno avuto qualsiasi precedente esposizione a ramucirumab - Pazienti con riscontro clinico o radiologico compatibile con polmonite interstiziale o fibrosi polmonare - Pazienti con interessamento del CNS non sono idonei |
|
E.5 End points |
E.5.1 | Primary end point(s) |
progression-free survival (PFS) |
Sopravvivenza libera dalla progressione della malattia (PFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
L'analisi primaria avra' inizio quando un evento PFS sara' riscontrato in circa l'80% dei pazienti arruolati |
Durante l'intera durata dello studio |
|
E.5.2 | Secondary end point(s) |
Serious adverse event, Adverse event, Safety laboratory assessments, Vital signs, overall response rate, Duration of response, Complete response, Cmax (maximum concentration), Cmin (minimum concentration) and Incidence of immunogenicity |
Evento avverdso serio, Evento avverso, valutazioni di laboratorio sulla sicurezza, segni vitali, tasso di risposta complessivo, durata della risposta, risposta completa, Cmax (concentrazione massima), Cmin (concentrazione minima) e incidenza dell'immunogenicita' |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout study. |
Durante l'intera durata dello studio |
|
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Therapeutic exploratory (Phase II) |
Valutazione terapeutica (Fase II) |
|
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Australia |
Japan |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
|
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
|
LVLS - Last visit or last scheduled procedure for the last patient. |
LVLS - Ultima visita o ultima procedura programmata per l'ultimo paziente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |