E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non small-cell lung cancer (NSCLC) |
carcinoma polmonare non a piccole cellule (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Non small-cell lung cancer |
tumore polmonare non a piccole cellule |
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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 | 14.1 |
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 demonstrate the antitumor activity of LDK378, as measured by overall response rate (ORR) to LDK378 by investigator assessment |
Dimostrare l’attività antitumorale di LDK378, misurando il tasso di risposta globale (ORR) a LDK378 mediante valutazione dello sperimentatore. |
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E.2.2 | Secondary objectives of the trial |
To evaluate response related endpoints as assessed by investigator and Blinded Independent Review Committee (BIRC): - Duration of response (DOR) - Disease control rate (DCR) - Time to response (TTR) To assess ORR by BIRC assessment To evaluate the safety profile of LDK378 To evaluate progression-free survival (PFS) To evaluate overall survival (OS) |
Giudicare gli endpoint correlati alla risposta valutati dallo sperimentatore e da un comitato di revisione indipendente in cieco (BIRC). Durata della risposta (DOR), tasso di controllo della malattia (DCR), tempo alla risposta (TTR) e determinare la ORR mediante valutazione del BIRC. Valutare il profilo di sicurezza d’impiego di LDK378 Valutare la sopravvivenza libera da progressione (PFS) Valutare la sopravvivenza globale (OS) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOKINETIC/PHARMACODYNAMIC: Vers:v00 Date:2012/08/03 Title:Additional biomarker research on tumor samples to evaluate changes in genes and proteins. Objectives:This study will provide important information to learn about the effect of LDK378 on the body and cancer.
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FARMACOCINETICA/FARMACODINAMICA: Vers:v00 Data:2012/08/03 Titolo:Valutazione degli indicatori biologici su campioni di tessuto tumorale, allo scopo di identificare le modificazioni nei geni e nelle proteine Obiettivi:Studiare l’effetto di LDK378 sull’organismo e sul tumore.
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E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC that carries an ALK rearrangement as per the FDAapproved FISH test (Abbott Molecular Inc) 2. Age 18 years or older at the time of informed consent. 3. Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose 4. Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC 5. Patients must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since. 6. Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study. Other protocol defined inclusion criteria may apply (7-12) |
1.Conferma istologica o citologica della diagnosi di NSCLC in stadio localmente avanzato o metastatico con riarrangiamento di ALK valutato in base al FISH test approvato dalla FDA (Abbott Molecular Inc). 2.Età uguale o superiore a 18 anni al momento del consenso informato. 3.I pazienti devono essere affetti da NSCLC in stadio localmente avanzato o metastatico che ha manifestato progressione durante terapia con crizotinib o entro 30 giorni dalla somministrazione dell’ultima dose. 4.I pazienti devono aver ricevuto chemioterapia citotossica per trattare il NSCLC in stadio localmente avanzato o metastatico. 5.I pazienti devono avere a disposizione un campione di tessuto tumorale archiviato, prelevato o al momento della diagnosi di NSCLC o in qualsiasi momento successivo. 6.I pazienti devono aver presentato risoluzione a Grado <= 2 di tutte le tossicità correlate alle terapie antitumorali precedenti. Questo criterio non si applica ai pazienti con nausea/vomito di Grado 2 e/o diarrea di Grado 2, nonostante terapia di supporto ottimale, ai quali non sarà consentito partecipare allo studio. Fare riferimento al protocollo per i rimanenti criteri (7-12) |
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E.4 | Principal exclusion criteria |
1. Patients with known hypersensitivity to any of the excipients of LDK378 2. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. 3. History of carcinomatous meningitis. 4. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. 5. Clinically significant, uncontrolled heart disease 6. Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug. Other protocol defined exclusion criteria may apply (7-19) |
1.Pazienti con ipersensibilità nota a uno qualsiasi degli eccipienti di LDK378. 2.Pazienti con metastasi sintomatiche del sistema nervoso centrale (SNC) che non sono stabili dal punto di vista neurologico o che hanno richiesto dosi crescenti di corticosteroidi nelle 2 settimane precedenti l’ingresso nello studio per la gestione dei sintomi del SNC. 3.Anamnesi positiva per meningite carcinomatosa. 4.Evidenza attuale o pregressa di neoplasia diversa da NSCLC che è stata diagnosticata e/o ha richiesto trattamento nei 3 anni precedenti. 5.Cardiopatia clinicamente rilevante, non controllata. 6.Terapia antitumorale sistemica somministrata successivamente all’ultima dose di crizotinib prima di iniziare la somministrazione del trattamento in studio. Fare riferimento al protocollo per i rimanenti criteri (7-19) |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR per RECIST v1.1 calculated as the proportion of patients with a best overall response defined as complete response or partial response (CR+PR) as assessed by investigator |
Tasso di risposta globale (ORR) secondo RECIST v1.1 a LDK378 calcolata come la proporzione di pazienti con una risposta globale definita come risposta completa o risposta parziale (CR+PR)mediante valutazione dello sperimentatore |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 cycles of 28 days up to 24 weeks |
Per sei cicli di 28 giorni fino a 24 settimane |
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E.5.2 | Secondary end point(s) |
- DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by investigator and BIRC - DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD, by investigator and BIRC - TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator and BIRC - ORR (CR+PR) per RECIST v1.1 as assessed by BIRC - Adverse events and laboratory abnormalities - PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by BIRC and investigator assessment - OS, defined as time from first dose of LDK378 to death due to any cause |
- DOR, calcolata come il tempo dalla data del prima documentata CR o PR alla prima progressione documentata o morte dovuta al tumore, mediante valutazione dello sperimentatore e del BIRC. - DCR, calcolata come la proporzione dei pazienti con la migliore risposta globale di CR, PR o SD, mediante valutazione dello sperimentatore e del BIRC. - TTR, calcolata come il tempo dalla prima dose di LDK378 alla prima risposta documentata (CR+PR), mediante valutazione dello sperimentatore e del BIRC. - ORR (CR+PR) secondo RECIST v1.1 mediante valutazione del BIRC. - Eventi avversi e alterazioni dei valori dei parametri di laboratorio. - PFS, definita come il tempo dalla prima dose di LDK378 alla progessione o morte dovuta a ogni tipo di causa, mediante valutazione dello sperimentatore e del BIRC. - OS, definita come il tempo dalla prima dose di LDK378 alla morte dovuta a ogni tipo di causa. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 cycles of 28 days up to 24 weeks for all |
Per sei cicli di 28 giorni fino a 24 settimane per tutti gli endpoint |
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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 | No |
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 | 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 | 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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | No |
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 |
Canada |
Hong Kong |
Japan |
Korea, Republic of |
Singapore |
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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The study will end once at least 75% of patients have died. Patients continuing to derive benefit from the study treatment at the end of the study in the opinion of the investigator will be able to continue receiving LDK378 on a separate protocol |
Lo studio terminerà quando almeno il 75% dei pazienti sarà deceduto. I pazienti che continuano a beneficare della terapia alla fine dello studio, a giudizio dello sperimentatore, potranno proseguire la terapia con LDK378 in uno studio separato. |
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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 | 20 |
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 | 20 |
E.8.9.2 | In all countries concerned by the trial days | 0 |