| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| stage III unresectable non-small cell lung cancer (NSCLC) |
| carcinoma del polmone non a piccole cellule (NSCLC) di stadio III non resecabile |
|
| E.1.1.1 | Medical condition in easily understood language |
| stage III unresectable non-small cell lung cancer (NSCLC) |
| carcinoma del polmone non a piccole cellule (NSCLC) di stadio III non resecabile |
|
| 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 | 10029519 |
| E.1.2 | Term | Non-small cell lung cancer stage III |
| 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 assess safety and tolerability of the proposed treatment strategy, as defined as proportion of patients with any Grade 3 and Grade 4 possibly related adverse events (PRAEs) within 6 months from the initiation of treatment |
| Valutare la sicurezza e la tollerabilità, come definito dagli eventi avversi possibilmente correlati di Grado 3 e Grado 4 (PRAE) entro sei mesi dall’inizio del trattamento |
|
| E.2.2 | Secondary objectives of the trial |
To assess the efficacy of the proposed treatment strategy in terms of Progression-Free Survival.
Endpoints:
¿ Median PFS according to RECIST 1.1 as assessed by the Investigator
¿ PFS12 (12 months) according to RECIST 1.1 as assessed by the Investigator
Other secondary objectives:
¿ Median OS and OS12 (12 months)
¿ Quality of life |
Valutare l’efficacia in termini di Progression-Free Survival.
Altri obiettivi secondari:
- Overall Survival
- Qualità di vita (mediante questionari EORTC QLQ C30 e LC13) |
|
| 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 ICF and in this protocol.
2 Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
3 18 years or older at the time of signing the ICF.
4 Histologically- or cytologically-documented NSCLC with locally-advanced, unresectable Stage III disease (according to the IASLC Staging Manual Version 8 [IASLC 2016]). Positron emission tomography (PET)/CT, MRI of the brain, and endobronchial ultrasound with biopsy are highly encouraged at diagnosis.
5 Patients with measurable disease assessed at baseline by CT/MRI will be entered in this study.
6 Must have a life expectancy of at least 12 weeks at enrolment.
7 WHO/ECOG PS 0-1.
8 Patient not eligible for concurrent chemo radiation according to investigator assessment
9 Adequate organ and marrow function at enrollment as defined below.
10 Body weight >30 kg at enrollment
11 Male or female.
12 Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
(a) Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
(b) Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy). |
1. Capacità di fornire il consenso informato firmato
2. Fornire il consenso informato scritto, firmato e datato prima di ogni procedura studio specifica obbligatoria, raccolta di campioni e analisi
3. 18 anni o più al momento della firma del consenso
4. Conferma istologica o citologica di NSCLC, localmente avanzato, Stadio III non resecabile (in accordo con IASLC Staging Manual Version 8 [IASLC 2016]). Tomografia a emissione di positroni (PET)/CT, MRI dell’encefalo, ed ecografia endobronchiale con biopsia sono altamente consigliate al momento della diagnosi
5. Malattia misurabile valutata al basale con CT/MRI
6. Aspettativa di vita di almeno 12 settimane al momento dell’arruolamento
7. WHO/ECOG PS 0-1
8. Paziente non eleggibile per concomitante chemio-radioterapia secondo la valutazione medica
9. Adeguata funzione d’organo e midollare al momento dell’arruolamento
10. Peso corporeo >30 Kg al momento dell’arruolamento
11. Maschio o femmina
12. Evidenza di post-menopausa, o test di gravidanza su urine o su siero negativo per le femmine in pre-menopausa. Le donne saranno considerate in post-menopausa se presentano amenorrea da 12 mesi in assenza di una causa medica alternativa. Si applicano i seguenti requisiti specifici per età:
(a) Donne <50 anni saranno considerate in post-menopausa se presentano amenorrea da 12 mesi o più a seguito della cessazione di trattamenti ormonali esogeni e se hanno livelli di ormone luteinizzante e ormone follicolo-stimolante nel range post-menopausale per l’Istituito o sono state sottoposte a sterilizzazione chirurgica (ovariectomia bilaterale o isterectomia)
(b) Donne =50 anni saranno considerate in post-menopausa se presentano amenorrea da 12 mesi o più a seguito della cessazione di tutti i trattamenti ormonali esogeni, hanno avuto menopausa indotta da radiazioni con ultime mestruazione >1 anno fa, hanno avuto menopausa indotta da chemioterapia con ultime mestruazione >1 anno fa, o sono state sottoposte a sterilizzazione chirurgica (ovariectomia bilaterale, salpingectomia bilaterale o isterectomia) |
|
| E.4 | Principal exclusion criteria |
1 Patients who have disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumors.
2 Mixed small-cell lung cancer and NSCLC histology.
3 History of allogeneic organ transplantation.
4 Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
(a) Patients with vitiligo or alopecia.
(b)Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
(c) Any chronic skin condition that does not require systemic therapy.
(d)Patients without active disease in the last 5 years at enrolment may be included but only after consultation with the Study Physician.
(e)Patients with celiac disease controlled by diet alone.
5 Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
6 History of another primary malignancy except for:
(a) Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence.
(b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
(c) Adequately treated carcinoma in situ without evidence of disease.
7 History of leptomeningeal carcinomatosis.
8 History of active primary immunodeficiency.
9 Active infection including hepatitis B (known positive hepatitis B surface antigen [HbsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
10 Any unresolved toxicity of NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
(a) Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
(b) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
11 Known allergy or hypersensitivity to durvalumab or any of the IP excipients.
Prior/concomitant therapy
12 Prior chemo-radiotherapy for lung cancer. Prior surgical resection (ie, Stage I or II) is permitted.
13 Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
see protocol |
1. Pazienti con malattia da considerare per il trattamento chirurgico come parte del loro piano di cura, come Pancoast o tumori del solco superiore
2. Carcinoma polmonare misto a piccole cellule e istologia NSCLC
3. Storia di trapianto d’organo allogenico
4. Disturbi autoimmuni o infiammatori attivi o documentati in precedenza (inclusa malattia infiammatoria intestinale [p. Es., Colite o morbo di Crohn], diverticolite [ad eccezione della diverticolosi], lupus eritematoso sistemico, sarcoidosi o sindrome di Wegener [granulomatosi con poliangite, morbo di Graves, artrite reumatoide, ipofisite, uveite, ecc]). Le seguenti sono eccezioni a questo criterio:
(a) Pazienti con vitiligine o alopecia
(b) Pazienti con ipotiroidismo (p. es., a seguito della sindrome di Hashimoto) stabile alla sostituzione ormonale
(c) Qualsiasi condizione cronica della pelle che non richiede terapia sistemica
(d) I pazienti senza malattia attiva negli ultimi 5 anni al momento dell'arruolamento possono essere inclusi ma solo dopo aver consultato il medico dello studio
(e) Pazienti con malattia celiaca controllata con la sola dieta
5. Malattia intercorrente non controllata, inclusa ma non limitata a infezione in corso o attiva, insufficienza cardiaca congestizia sintomatica, ipertensione non controllata, angina pectoris instabile, aritmia cardiaca, ILD, gravi condizioni gastrointestinali croniche associate a diarrea, o malattie psichiatriche / situazioni sociali che limiterebbero il rispetto dei requisiti dello studio, che aumentano sostanzialmente il rischio di incorrere in eventi avversi o compromette la capacità del paziente di fornire il consenso informato scritto
6. Storia di un altro tumore maligno primario ad eccezione di:
(a) Malignità trattata con intento curativo e assenza di malattia attiva nota da =5 anni prima della prima dose di IP e con basso rischio potenziale di recidiva
(b) Cancro della pelle non melanoma adeguatamente trattato o lentigo maligna senza evidenza di malattia
(c) Carcinoma adeguatamente trattato in situ senza evidenza di malattia
7. Storia di carcinomatosi leptomeningea
8. Storia di immunodeficienza primaria attiva
9. Infezione attiva inclusa epatite B (nota positività riguardo l'antigene di superficie dell'epatite B [HbsAg]), virus dell'epatite C (HCV) o virus dell'immunodeficienza umana (HIV) (anticorpi HIV 1/2 positivi).
Sono idonei i pazienti con infezione pregressa o risolta da virus dell'epatite B (HBV) (definita come presenza di anticorpi core dell'epatite B [anti-HBc] e assenza di HbsAg). I pazienti positivi per l'anticorpo dell'epatite C sono eleggibili solo se la reazione a catena della polimerasi è negativa per l'acido ribonucleico (RNA) dell'HCV
10. Qualsiasi tossicità non risolta con NCI CTCAE grado =2 da precedente terapia antitumorale ad eccezione di alopecia, vitiligine e valori di laboratorio definiti nei criteri di inclusione
(a) I pazienti con neuropatia di Grado =2 saranno valutati caso per caso dopo aver consultato il medico dello studio
(b) I pazienti con tossicità irreversibile che ragionevolmente non si prevede possa essere esacerbata dal trattamento con durvalumab possono essere inclusi solo dopo aver consultato il medico dello studio
11. Nota allergia o ipersensibilità al durvalumab o a qualsiasi degli eccipienti dell’IP
12. Precedente chemio-radioterapia per tumore al polmone. Precedente resezione chirurgica (es. Stadio I o II) è consentita
13. Somministrazione di vaccini vivi attenuati nei 30 giorni precedenti la prima dose di IP
Nota: i pazienti, se arruolati, non devono ricevere vaccini vivi durante il trattamento con IP e fino a 30 giorni dopo l'ultima dose di IP
Ulteriori criteri in protocollo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Grade 3 and Grade 4 PRAEs |
| incidenza di PRAE di grado 3 e 4 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| in aperto, a singolo braccio |
| open label, single arm |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 3 |
| 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 | Information not present in EudraCT |
| 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 | 3 |
| 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 | 3 |
| 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 |
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