E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced and/or metastatic malignant tumor (anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, papillary renal cell carcinoma type 1, alveolar soft part sarcoma, clear cell sarcoma or alveolar rhabdomyosarcoma) deemed incurable by conventional surgery, radiotherapy, systemic therapy or any other means |
Localmente avanzato e / o metastatico tumore maligno (linfoma anaplastico a grandi cellule, tumore infiammatorio miofibroblastico, papillare renale carcinoma a cellule di tipo 1, sarcoma alveolare mollica, sarcoma a cellule chiare o rabdomiosarcoma alveolare) ritenuto incurabile dalla chirurgia tradizionale, radioterapia, terapia sistemica o di qualsiasi altro mezzi |
|
E.1.1.1 | Medical condition in easily understood language |
Local diagnosis of locally advanced and/or metastatic sub types of lymphoma, RCC and soft tissue sarcoma deemed incurable by surgery, radiotherapy, systemic therapy or any other means. |
Diagnosi locale di sottotipi localmente avanzato e / o metastatico di linfoma, sarcoma dei tessuti molli RCC e ritenuto incurabile dalla chirurgia, radioterapia, terapia sistemica o qualsia |
|
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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065867 |
E.1.2 | Term | Alveolar rhabdomyosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002227 |
E.1.2 | Term | Anaplastic large cell lymphoma T- and null-cell types |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001882 |
E.1.2 | Term | Alveolar soft part sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 |
The study zill primarily assess the efficacy of crizotinib in a variety of tumors zith alterations in ALK and/or MET pathways. The targeted patient population zill include patients zith tumors harboing specific alterations leading to ALK and/or MET activation,where tyrosine kinase inhibitors against these targets have not yet been adequately explored. |
Lo studio Zill principalmente valutare l'efficacia di crizotinib in una varietà di tumori alterazioni zith in ALK e / o TEM percorsi. Il mirata Zill popolazione di pazienti sono i tumori dei pazienti zith harboing specifiche alterazioni che portano alla ALK e / o attivazione MET, in cui gli inibitori della tirosin-chinasi nei confronti di questi obiettivi non sono ancora adeguatamente esplorato. |
|
E.2.2 | Secondary objectives of the trial |
To study the specificity of the kinase inhibitor for tumors in all cohorts by explorative comparison of treatment results in patients with the same disease type with and without genetic alterations in ALK and/or MET. To investigate sensitive and reliable methodologies for patient screening for such defects, to be potentially cross-validated and further developed by an accredited laboratory in later steps, based on prospectively collected biological material from this trial. To explore whether molecularly driven, high quality multi-tumor screening Phase II trials are feasible in a multiinstitutional, multidisciplinary setting, when screening and tratment are perfor;ed by EORTC (+:-additional selected sites). To study soluble serum factors leading to MET pathway activation as predictive biomarkers for response to tratment. |
Per studiare la specificità della chinasi per tumori in tutti coorti rispetto esplorativa dei risultati del trattamento in pazienti con la stessa malattia tipo con e senza alterazioni genetiche in ALK e / o TEM. Per studiare metodologie sensibili ed affidabili per lo screening dei pazienti per tali difetti, per essere potenzialmente cross-validati e ulteriormente sviluppato da un laboratorio accreditato nei passaggi successivi, sulla base di materiale biologico raccolti prospetticamente da questa prova. Per esplorare zhether molecolarmente orientata, di alta qualità multi-tumorali di screening studi di Fase II sono fattibili in un multi-istituzionale, l'impostazione multidisciplinare, quando lo screening e il tratamento sono prestazioni, ed da EORTC.Studiare i fattori solubili del siero che portano alla via di attivazione MET come biomarcatori predittivi di risposta al tratamento. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Step 1 registration: *Local diagnosis of locally advanced and/or metastatic malignant tumor (defined befor) deemed incurable by conventional surgery, radiotherapy, systemic therapy or any other means.* Mandatory shipment of tumor-containing tissue blocks. Step 2 registration: *Measurable disease according to RECIST 1.1 with target lesion of at least 20mm (or 10mm on spiral CT scans). *Minimum age 15 years, no upper age limit. *Eastern Cooperative OncologyGroup (ECOG) performance status 0-2. *Adequate hematological function:ANC≥1x109/L, platelets≥30x109/L and hemoglobin≥8g/dl. *Adequate renal function:serum creatinine ≤2xULN.*Adequeta liver function:Bilirubin ≤1.5xULN. AST and ALT≤2.5xULN in the qbsence of liver metastases and ≤5xULN if liver function abnormalities are due to the underlying malignancy. *Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule;those conditions should be discussed with the patient before registration in te trial. *Negative pregnancy test. *All patients (male and female) of childbearing/reproduxtive potential must use adequate birth control measures during the study treatment period and for at least three months after the last study tratment. *Written consent before registration. *Additional inclusion criteria linked to specific tumor type are described in the protocol in section 3.2 |
Passaggio 1 registrazione: diagnosi * locale di localmente avanzato e / o metastatico tumore maligno (definito befor) ritenuto incurabile dalla chirurgia tradizionale, radioterapia, terapia sistemica o qualsiasi altro mezzo spedizione * obbligatorio di tumore contenenti blocchi di tessuto.. Fase 2 di registrazione: * malattia misurabile secondo i criteri RECIST 1.1 con lesione bersaglio di almeno 20 mm (o 10 mm in TC spirale). * Età minima 15 anni, senza limiti di età superiore. * Eastern Cooperative OncologyGroup (ECOG) performance status 0-2. * Funzione adeguata ematologiche: ANC ≥ 1x109 / L, piastrine ≥ 30x109 / L e di emoglobina ≥ 8g/dl. * Funzione renale adeguata:. Creatinina sierica ≤ 2xULN * funzionalità epatica Adequeta: Bilirubina ≤ 1.5xULN. AST e ALT ≤ 2.5xULN nel qbsence di metastasi epatiche e 5xULN ≤ se alterazioni della funzionalità epatica sono dovuti al tumore di base. * Assenza di qualsiasi psicologica, familiare, condizione sociologica o geografica potenzialmente ostacolano il rispetto del protocollo di studio e follow-up calendario; tali condizioni deve essere discussa con il paziente prima della registrazione nella prova te. * Test di gravidanza negativo. * Tutti i pazienti (uomini e donne) in età fertile / reproduxtive devono utilizzare adeguate misure contraccettive durante il periodo di trattamento dello studio e per almeno tre mesi dopo al trattamento ultimo studio. * Consenso scritto prima della registrazione. Criteri di inclusione * supplementari legate al tipo specifico di tumore sono descritti nel protocollo nella sezione 3.2 |
|
E.4 | Principal exclusion criteria |
Step 2 registration: *Carcinomatous meningitis or leptomeningeal disease. *Treatment zith any other investigational drug within the past 4 weeks or within less than 4 half-life times of the investigational drug before tratment with crizotinib (whatever is the longest period). *Prior therapy directly targeting ALK and/or MET, previous tratment with crizotinib.*Previous and active malignancy for the last three years with the exception of non-melanoma skin cancer, localized cervical cancer, localized and presumably cured prostate cancer or adequately treatedbasal or squamous cell skin carcinoma. *Acute or chronic severe gastrointestinal conditions such as diarrhea or ulcer. *Current congestive heart failure. *Ongoing cardiac dysrhythmias of NCI CTCAE Grade >2. *Uncontrolled atrial fibrillation of any grade. *Pregnant women. |
Passaggio 2 di registrazione: * meningite carcinomatosa o malattia leptomeningea. * Il trattamento zith qualsiasi altro farmaco sperimentale nelle ultime 4 settimane o in meno di 4 volte l'emivita del farmaco in fase di sperimentazione prima di tratamento con crizotinib (qualunque sia il periodo più lungo). * La terapia preventiva di mira direttamente ALK e / o MET, tratamento precedente con crizotinib. * Malignità precedente e attiva per gli ultimi tre anni, con l'eccezione di non-melanoma, cancro della pelle, localizzato il cancro cervicale, localizzato e presumibilmente curato il cancro alla prostata o adeguatamente treatedbasal o carcinoma a cellule squamose della pelle. * Gravi condizioni acute o croniche gastrointestinali come diarrea o ulcera. * Corrente insufficienza cardiaca congestizia. * In corso di aritmie cardiache di grado NCI CTCAE> 2. * Fibrillazione atriale non controllata di qualsiasi grado. * Le donne in gravidanza. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Response rate documented by RECIST 1.1 (with response confirmation). |
Tasso di risposta documentato secondo i criteri RECIST 1.1 (con conferma di risposta) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of trial (per cohort) |
Alla fine della prova (per coorte) |
|
E.5.2 | Secondary end point(s) |
Safety (CTAE v4.0) Progression free survival Clinical benefit, as assessed by the rate of CR+PR+Stable Disease (SD) Overall survival Duration of clinical benefit |
•Sicurezza (CTAE v 4.0) •Sopravvivenza libera da progressione •Tasso di controllo della malattia •Sopravvivenza globale •Durata della risposta •Endpoint di ricerche correlate Sicurezza:Eventi avversi, farmaci concomitanti ed esami di laboratorio. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the end of the trial (per cohort) |
Alla fine del processo (per coorte) |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Translational research |
Ricerca traslazionale |
|
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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
|
End of study occurs when all of the following criteria have been satisfied:1.Thirty days after all patients have stopped protocol treatment.2.The trial is mature for the analysis of the primary endpoint as defined in the protocol, if the trial reaches its primary endpoint.3.The database has been fully cleaned and frozen for this analysis. |
1.Thirty giorno dopo che tutti i pazienti hanno smesso di protocollo di sperimentazione treatment.2.Il processo è maturo per l'analisi dell'endpoint primario come definito nel protocollo.3.The primaria è stata pulita e congelati per l'analisi. |
|
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 | 6 |
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 |