E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pretreated metastatic non-small-cell lung cancer with MET amplification or ROS1 translocation |
Tumore pretrattato al polmone non a piccole cellule con amplificazione MET o traslocazione ROS |
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E.1.1.1 | Medical condition in easily understood language |
Pretreated metastatic non-small-cell lung cancer with MET amplification or ROS1 translocation |
Tumore pretrattato al polmone non a piccole cellule con amplificazione MET o traslocazione ROS |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 |
To assess the efficacy and safety and tolerability of Crizotinib in pretreated metastatic non-small-cell lung cancer with MET amplification or ROS1 translocation |
Valutare l’efficacia, la sicurezza e la tollerabilità del Crizotinib nel tumore pretrattato al polmone non a piccole cellule con amplificazione MET o traslocazione ROS1 |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Non Applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed diagnosis of NSCLC
• Availability of tumor tissue for ROS1, and MET analyses
• Patient positive for ROS1 translocation or MET amplification
• Radiological measurable disease according to RECIST criteria
• At least 1 previous standard chemotherapy regimen
• Performance status 0-2 (ECOG)
• Patient compliance to trial procedures
• Age ≥ 18 years
• Written informed consent |
• Diagnosi di NSCLC confermata istologicamente
• Disponibilità di tessuto tumorale per le analisi di ROS1 e MET
• Paziente positivo per la traslocazione ROS1 o per l’amplificazione MET
• Malattia misurabile radiologicamente in accordo ai criteri RECIST
• Almeno 1 regime precedente di chemioterapia standard
• Performance status 0-2 (ECOG)
• Compliance del paziente alle procedure cliniche
• Età ≥ 18 anni
• Consenso informato scritto
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E.4 | Principal exclusion criteria |
• No tumor tissue available or patient negative for ROS1 translocation or MET amplification
• Absence of any measurable lesions
• For ROS1+ patients: Previous therapy with crizotinib or any anti-ALK agents
• For MET amplified patients: Evidence of MET amplification in tumor tissue collected in EGFR mutant patient at time of EGFR-TKI acquired resistance occurrence. An EGFR mutant patient is eligible if MET amplification is detected in a tumor specimen collected before starting an EGFR-TKI
• No previous chemotherapy
• Concomitant radiotherapy or chemotherapy
• Symptomatic brain metastases
• Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and cutaneous squamous cell carcinoma
• Pregnancy or lactating |
ancata disponibilità di tessuto tumorale o paziente negativo alla traslocazione ROS1 o all’amplificazione MET
• Assenza di qualsiasi lesione misurabile
• Per i pazienti ROS1: terapia precedente con crizotinib o qualsiasi agente anti- ALK
• Per i pazienti MET amplificati: evidenza di amplificazione MET in tessuto tumorale prelevato da pazienti EGFR mutati al momento del verificarsi della resistenza acquisita all’EGFR-TKI. Un paziente EGFR mutato è eleggibile se l’amplificazione MET è rilevata in un campione tumorale prelevato prima di iniziare un EGFR-TKI
• Nessuna chemioterapia precedente
• Radioterapia o chemioterapia concomitante
• Metastasi cerebrali sintomatiche
• Diagnosi di qualsiasi altro tumore maligno durante gli ultimi cinque anni, eccetto per il carcinoma in situ della cervice uterina e per il carcinoma della pelle a cellule squamose
• Gravidanza o allattamento |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-Primary:
• Response rate to crizotinib in patients with ROS1 translocation or MET amplification
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Co-primario:
• Tasso di risposta al crizotinib in pazienti con traslocazione ROS1 o amplificazione MET
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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) |
• Sopravvivenza libera da progressione (PFS)
• Sopravvivenza globale (OS)
• Tossicità
• Correlazione con biomarkers tumorali addizionali in tessuti tumorali o nel sangue
• Risposta in accordo con i diversi livelli di traslocazione ROS1 o amplificazione MET (ratio>2.2 e <5 contro ratio ≥5) |
• Progression-free survival (PFS)
• Overall Survival (OS)
• Toxicity
• Correlation with additional tumor biomarkers in tumor tissue or blood
• Response according to different levels of ROS1 translocation or MET amplification (ratio >2.2 and <5 versus ratio ≥ 5)
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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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 25 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |