| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-Small Cell Lung Cancer |
| Tumore ai polmoni non a piccole cellule |
|
| E.1.1.1 | Medical condition in easily understood language |
| EGFRm locally adv or metastatic Non-Small Cell Lung Cancer |
| Tumore ai polmoni non a piccole cellule localmente avanzato o metastatico EGFRm |
|
| 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 | 21.1 |
| 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) |
|
| 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 compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on PFS |
| Confrontare l’efficacia della chemioterapia più il trattamento con osimertinib rispetto alla chemioterapia più placebo in base alla PFS |
|
| E.2.2 | Secondary objectives of the trial |
To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on intracranial PFS in patients with baseline brain metastases and patients without baseline brain metastases
To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on extracranial PFS
To compare the efficacy of chemotherapy plus osimertinib treatment relative to chemotherapy plus placebo based on OS |
Confrontare l’efficacia della chemioterapia più il trattamento con osimertinib rispetto alla chemioterapia più placebo in base alla PFS
intracranica in pazienti con metastasi cerebrali al basale e pazienti senza metastasi cerebrali al basale
Confrontare l’efficacia della chemioterapia più il trattamento con osimertinib rispetto alla chemioterapia più placebo in base alla PFS
extracranica
Confrontare l’efficacia della chemioterapia più il trattamento con osimertinib rispetto alla chemioterapia più placebo in base alla OS |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
2) Pathologically confirmed non-squamous NSCLC (Non-small cell lung cancer )
3) Locally advanced (clinical stage IIIB or IIIC) or metastatic NSCLC (clinical stage IVA or IVB) or recurrent NSCLC, not amenable to curative surgery or radiotherapy.
4) Evidence of radiological extracranial disease progression following response with first line osimertinib treatment but who have not received further, subsequent treatment.
5) World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
6) Life expectancy >12 weeks at Day 1.
7) At least 1 lesion, not previously irradiated.
8) Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling criteria at screening.
9) Male patients must be willing to use barrier contraception |
1)Capace di sottoscrivere il informato firmato, che include la conformità con i requisiti e le restrizioni elencati nel consenso informato e in questo protocollo.
2)NSCLC (Tumore al polmone non a piccole cellule) non squamoso patologicamente confermato
3) NSCLC localmente avanzato (stadio clinico IIIB o IIIC) o metastatico (stadio clinico IVA o IVB) o NSCLC ricorrente, non suscettibile a chirurgia curativa o radioterapia.
4) Evidenza della progressione radiologica extracranica della malattia in seguito alla risposta con il trattamento in prima linea con osimertinib ma che non ha ricevuto successivo, ulteriore trattamento.
5) World Health Organization status di performance da 0 a 1 allo screening senza nessuna deteriorazione clinica significativa nelle precedenti 2 settimane.
6) Aspettativa di vita > 12 settimane al giorno 1
7) Almeno una lesione, non precedentemente irradiata;
8) Le donne devono utilizzare misure contraccettive altamente efficienti, e devono avere un test di gravidanza negativo prima dell’inizio del dosaggio se fertili, o devono dimostrare evidenza di non essere fertili soddisfacendo i criteri allo screening.
9) I pazienti di sesso maschile devono essere disposti ad utilizzare metodi contraccettivi di barriera. |
|
| E.4 | Principal exclusion criteria |
- Clinical or radiological evidence of CNS progression on first-line osimertinib
- Past medical history of ILD/pneumonitis, drug-induced ILD/pneumonitis, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis
- Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of IP
- Any unresolved toxicities from prior extracranial therapy (eg, adjuvant chemotherapy) greater than CTCAE Grade 1 at the time of starting IP, with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy.
- More than 4 weeks elapsed since last dose of osimertinib by date of randomization |
-Evidenza Clinica o radiologica della progressione CNS di osimertinib first-line
-Pregresse IDL/polmoniti, IDL/polmoniti farmacologiche, polmoniti da radiazioni che hanno richiesto il trattamento con steroidi, o qualsiasi evidenza di IDL/polmonite clinicamente attiva
-Qualsiasi malignità concomitante e/o attiva che richiede il trattamento entro 2 anni dalla prima dose di IP
-Qualsiasi tossicità irrisolta da precedente terapia extracraniale (es. chemioterapia adiuvante) maggiore di CTCAE Grado 1 al momento dell’inizio IP, ad eccezione dell’alopecia e Grado2 precedente a neuropatia relativa a platino-terapia.
- Sono trascorse più di 4 settimane dall'ultima dose di osimertinib per data di randomizzazione |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
PFS is defined as time from randomization until progression (intracranial or extracranial, whichever occurs first) per RECIST 1.1 (for extracranial progression) and CNS RECIST 1.1 (for intracranial progression) as assessed by the Investigator at local site or death due to
any cause. |
| La PFS è definita come il tempo che intercorre dalla randomizzazione fino alla progressione (intracranica o extracranica, a seconda di quale evento si verifichi prima) secondo i RECIST 1.1 (per la progressione extracranica) e secondo i RECIST 1.1 per l’SNC (per la progressione intracranica) come valutato dallo Sperimentatore presso il centro locale o fino al decesso per qualsiasi causa |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Approximately 39 months after the first patient is randomized. |
| Approssimativamente 39 mesi dopo che il primo paziente è randomizzato. |
|
| E.5.2 | Secondary end point(s) |
Intracranial PFS is defined as time from randomization until intracranial progression per CNS RECIST 1.1 as assessed by the Investigator at local site or death due to any cause
Extracranial PFS is defined as time from randomization until extracranial progression per RECIST 1.1 as assessed by the Investigator at local site or death due to any cause
OS is defined as the length of time from randomization until the date of death due to any cause |
La PFS intracranica è definita come il tempo che intercorre dalla randomizzazione fino alla progressione intracranica secondo i RECIST 1.1 per l’SNC come valutato dallo Sperimentatore presso il centro locale o fino al decesso per qualsiasi causa
La PFS extracranica è definita come il tempo che intercorre dalla randomizzazione fino alla progressione extracranica secondo i criteri RECIST 1.1 come valutato dallo Sperimentatore presso il centro locale o fino al decesso per qualsiasi causa
L’OS è definita come l’intervallo di tempo trascorso dalla data della randomizzazione al decesso per qualsiasi causa |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Approximately 45 months after the first patient is randomized |
| Approssimativamente 45 mesi dopo che il primo paziente è randomizzato |
|
| 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) | 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 |
| China |
| Israel |
| United States |
| Austria |
| Germany |
| Italy |
| Spain |
|
| 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
|
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned days | 16 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 13 |
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