| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| non small cell lung cancer |
| tumore non a piccole cellule del polmone |
|
| E.1.1.1 | Medical condition in easily understood language |
| non small cell lung cancer |
| tumore non a piccole cellule del polmone |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10062042 |
| E.1.2 | Term | Lung neoplasm |
| 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 |
investigate which is the best combination temporal treatment of chemotherapy and radiotherapy in patients undergoing resection
Surgery for NSCLC pN2.
compare directly postoperative radiotherapy and sequential or concomitant chemotherapy in patients with NSCLC pN2,
- Evaluation of the incidence and degree of acute oesophageal toxicity according to the CTCAE criteria version 4.0
- Evaluation of survival free from locoregional relapse |
L’obiettivo dello studio è quello di indagare quale sia la migliore combinazione
temporale di trattamento chemioterapico e radioterapico(chemioterapia sequenziale o concomitante) nei pazienti sottoposti a resezione
chirurgica per NSCLC pN2.
Valutazione e confronto dell’incidenza e del grado di tossicità acuta esofagea (entro i primi
4 mesi dal termine del trattamento) definita secondo i criteri CTCAE versione 4.0
Valutazione e confronto di sopravvivenza libera da ricaduta locoregionale |
|
| E.2.2 | Secondary objectives of the trial |
Evaluation of overall survival (Overall survival, OS), survival cause
specific (disease specific survival, DSS) progression-free survival (progression
free survival, PFS), survival free from distant metastases (freedom from distant
metasis, FFDM).
Evaluation a of acute pulmonary and cardiac toxicity (within 30 days from
term of treatment defined according to the CTCAE criteria)
Evaluation of defined late pulmonary, cardiac and esophageal toxicity
according to the CTCAE criteria version 4.0 |
Valutazione sopravvivenza globale (Overall survival, OS), sopravvivenza causa
specifica (disease specific survival, DSS) sopravvivenza libera da progressione (progression
free survival, PFS), sopravvivenza libera da metastasi a distanza (freedom from distant
metasis, FFDM).
Valutazione tossicità polmonare e cardiaca acuta (entro i 30 giorni dal termine del trattamento definite secondo i criteri CTCAE)
Valutazione tossicità polmonare, cardiaca ed esofagea tardiva definita
secondo i criteri CTCAE versione 4.0 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patients between the ages of 18 and 75.
Patients with NSCLC with a stologically proven diagnosis.
Clinically non-metastatic patients at a distance (CT or MRI negative for metastases
cerebral, chest CT complete abdomen or PET-CT with 18 fluorine-desoxy-glucose negative for
distant metastasis) before enrollment
Patients undergoing lobectomy or sublobar resection and ilo-medistinic lymphadenectomy.
Patients treated surgically with macroscopically radical resection (R0-R1) with mediastinal lymph node involvement (pN2), any stage of T.
ECOG Performance Status 0-1
No other surgical, chemotherapy or radiotherapy treatments for neoplasia, except of non-melanoma tumors of the skin or in situ tumor of the cervix and other solid tumors
which radical treatment was completed at least three years before it was entered into
study and for which the patient has remained continuously free of disease.
Signature of informed consent.
Possibility of access to follow-up.
Preoperative systemic staging with chest CT, full abdomen CT, brain CT with
contrast medium or alternatively brain NMR without and with contrast medium or PET 18FDG and TC
brain with contrast medium or MRI (performed within 90 days prior to randomization).
Interval between surgery and start of treatment not exceeding 60 days |
Pazienti di età compresa tra i 18 e 75 anni.
Pazienti affetti da NSCLC con diagnosi dimostrata stologicamente.
Pazienti clinicamente non metastatici a distanza (TC o RM encefalo negativa per metastasi
cerebrali, TC torace addome completo o PET-TC con 18 Fluoro-desossi-glucosio negativa per
metastasi a distanza) prima dell’arruolamento
Pazienti sottoposti a lobectomia o resezione sublobare e linfoadenectomia ilo-medistinica.
Pazienti trattati chirurgicamente con resezione macroscopicamente radicale (R0-R1) con
riscontro di interessamento linfonodale mediastinico (pN2), qualsiasi stadio di T.
Performance Status ECOG 0-1
Non altri trattamenti chirurgici, chemioterapici o radioterapici per neoplasie, ad eccezione
di tumori non-melanoma della cute o di tumore in situ della cervice e di altri tumori solidi il
cui trattamento radicale sia stato completato almeno tre anni prima dell’arruolamento in
studio e per i quali il paziente sia rimasto continuativamente libero da malattia.
Firma del consenso informato.
Possibilità di avere accesso al follow-up.
Staging sistemico pre-operatorio con TC torace, TC addome completo, TC encefalo con mezzo di contrasto o in alternativa RMN encefalo senza e con mdc oppure PET 18FDG e TC
encefalo con mdc o RMN (eseguiti nei 90 giorni precedenti la randomizzazione).
Intervallo tra chirurgia e inizio del trattamento non superiore a 60 giorni. |
|
| E.4 | Principal exclusion criteria |
Metastatic disease for pre-operative investigations.
cN3 finding at pre-surgery staging exams.
Patients undergoing neoadjuvant chemotherapy (pre-surgery).
Respiratory function tests (PFR) with FEV1 <1.5 liters or DLCO <50% predicted.
Chronic hepatic failure in stage B and C according to Child-Pugh classification.
Grade IV kidney failure (creatinine clearance <30 ml / min).
Pregnancy or breastfeeding.
allergy to the study drugs or to the excipients used in them
formulation
One of the following conditions:
- Myocardial infarction in the 12 months prior to randomization
- Severe congestive heart failure (NYHA class III-IV)
- Unstable angina
- Cardiomyopathy in progress
- Ventricular arrhythmia
- Uncontrolled arterial hypertension
- Uncontrolled diabetes
- Serious psychotic disorders in progress
- Severe infection in progress
- Any other serious illness that could interfere with the administration
of the therapy foreseen by the protocol |
Malattia metastatica agli accertamenti pre-operatori.
Riscontro cN3 agli esami di stadiazione pre-chirurgia.
Pazienti sottoposti a chemioterapia neoadiuvante (pre-chirurgia).
Prove di funzionalità respiratoria (PFR) con FEV1 < 1.5 litri o DLCO < 50% del predetto.
Insufficienza epatica cronica in stadio B e C secondo classificazione Child-Pugh.
Insufficienza renale di grado IV (Clearance della creatinina < 30 ml/min).
Gravidanza o allattamento.
Presenza di allergia nota ai farmaci in studio o agli eccipienti impiegati nella loro
formulazione
Una delle seguenti condizioni:
- Infarto del miocardio nei 12 mesi precedenti la randomizzazione
- Insufficienza cardiaca congestizia grave (NYHA cl. III-IV)
- Angina instabile
- Cardiomiopatia in atto
- Aritmia ventricolare
- Ipertensione arteriosa non controllata
- Diabete non controllato
- Disordini psicotici gravi in atto
- Grave infezione in atto
- Qualsiasi altra grave infermità che possa interferire con la somministrazione
della terapia prevista dal protocollo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy endpoint: Evaluation and comparison of locoregional relapse-free survival
Toxicity endpoint: evaluation and comparison of the incidence and degree of acute esophageal toxicity (within the first 4 months from the end of the treatment) according to the CTCAE version 4.0 criteria |
Endpoint di Efficacia: Valutazione e confronto di sopravvivenza libera da ricaduta locoregionale
Endpoint di tossicità: Valutazione e confronto dell’incidenza e del grado di tossicità acuta esofagea (entro i primi 4 mesi dal termine del trattamento) definita secondo i criteri CTCAE versione 4.0 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy point: at each check
Toxicity endpoint: 4th month and at each check |
Endpoint di Efficacia: ad ogni controllo
Endpoint di tossicità: 4° mese e ad ogni controllo |
|
| E.5.2 | Secondary end point(s) |
| Efficacy Overall survival, OS, sdisease specific survival, DSSprogression free survival, PFS,freedom from distant metasis, FFDM |
| • Endpoint di Efficacia: Valutazione e confronto di sopravvivenza globale , sopravvivenza causa specifica sopravvivenza libera da progressione , sopravvivenza libera da metastasi a distanza . |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| at each check |
| ad ogni controllo |
|
| 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 | No |
| E.6.5 | Efficacy | No |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| radiochemioterapia adiuvante, concomitante |
| Adjuvant RadioChemotherapy, concomitant |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| farmaci chemioterapici più radiochemioterapia adiuvante o sequenziale |
| Chemotherapy drugs and Adjuvant RadioChemotherapy or Sequential |
|
| 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 | 13 |
| 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 | 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 8 |
| 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 | 8 |
| 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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