E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
unresectable stage III non-small cell lung cancer
(NSCLC) |
carcinoma polmonare non a piccole cellule (NSCLC) di stadio III non resecabile |
|
E.1.1.1 | Medical condition in easily understood language |
unresectable stage III non-small cell lung cancer
(NSCLC) |
carcinoma polmonare 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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025052 |
E.1.2 | Term | Lung cancer non-small cell stage III |
E.1.2 | System Organ Class | 100000004864 |
|
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 overall survival (OS) time by treatment arm |
Confrontare il tempo di sopravvivenza complessiva (overall survival, OS) per braccio di trattamento. |
|
E.2.2 | Secondary objectives of the trial |
- Time to symptom progression (TTSP) as measured by the Lung Cancer
Symptom Scale (LCSS).
- Progression-free survival (PFS) time.
- Time to progression (TTP).
- Safety. |
- Tempo alla progressione dei sintomi (time to symptom progression, TTSP) come misurato mediante la Scala di valutazione della sintomatologia del carcinoma polmonare (Lung Cancer Symptom Scale, LCSS).
- Tempo di sopravvivenza libera da progressione (progression-free survival, PFS).
- Tempo alla progressione (time to progression, TTP).
- Sicurezza.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Written informed consent, before any trial-related activities are
carried out.
2) Histologically or cytologically documented unresectable stage III
NSCLC, including bronchioalveolar carcinomas. Cancer stage must be
confirmed and documented by computed tomography (CT), magnetic
resonance imaging (MRI) or positron emission tomography (PET) scan.
3) Prior concurrent CRT which is defined as follows:
- Minimum of 2 cycles of platinum-based chemotherapy.
- Radiotherapy with total tumor dose ≥ 60 Gray (Gy) and a single
fraction dose ≥ 1.8 Gy.
- Overlap of radiotherapy with minimum 2 cycles of platinum-based
chemotherapy (one cycle is defined as either 3 or 4 weeks depending on
the
chemotherapy regimen).
4) Documented stable disease or objective response, according to
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, after primary
concurrent CRT for unresectable stage III disease, within 4 weeks (28
days) prior to randomization
5) An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6) A platelet count, white blood cells (WBC) and hemoglobin value as
defined in the protocol.
7) Male or female,
8) 18 years of age or over.
Other protocol defined inclusion criteria could apply. |
- Consenso informato scritto, prima che venga avviata qualsiasi attività relativa allo studio.
- NSCLC di stadio III non resecabile istologicamente o citologicamente documentato, compresi i carcinomi bronchioloalveolari. Lo stadio del tumore deve essere confermato e documentato da tomografia assiale computerizzata (TAC), risonanza magnetica (RMI) o scansione tomografica a emissione di positroni (PET).
- CRT concomitante precedente è definita come segue:
• Un minimo di 2 cicli di chemioterapia a base di platino.
• Radioterapia con una dose tumorale totale ≥ 60 Gray (Gy) e una singola dose frazionata ≥ 1.8 Gy.
• Sovrapposizione di radioterapia con minimo 2 cicli di chemioterapia a base di platino (un ciclo è definito come 3 o 4 settimane a seconda del regime chemioterapico).
• Stabilizzazione della malattia o risposta obiettiva documentata, secondo i criteri di valutazione della risposta nei tumori solidi (Response Evaluation Criteria in Solid Tumors, RECIST) 1.1, dopo CRT concomitante primaria per malattia in stadio III non resecabile, entro le 4 settimane (28 giorni) precedenti alla randomizzazione.
• Uno stato di validità ECOG pari a 0-1.
• Una conta piastrinica, valori dei globuli bianchi ed emoglobina come definito da protocollo.
• Maschi o femmine
• ≥ di 18 anni di età.
Altri criteri di inclusione definiti nel protocollo potrebbero applicarsi.
|
|
E.4 | Principal exclusion criteria |
1) Undergone lung cancer specific therapy (including surgery) other
than initial concurrent CRT.
2) Received chemotherapy during radiotherapy in radiosensitizing doses
only.
3) Metastatic disease.
4) Malignant pleural effusion at initial diagnosis, during initial CRT,
and/or at trial entry.
5) Past or current history of neoplasm other than lung carcinoma, except
for curatively treated nonmelanoma skin cancer, in situ carcinoma of the
cervix or other cancer curatively treated and with no evidence of disease
for at least 5 years.
6) A recognized immunodeficiency disease including human
immunodeficiency virus (HIV) infection and other cellular
immunodeficiencies, hypogammaglobulinemia or
dysgammaglobulinemia; subjects who have hereditary, congenital or
acquired immunodeficiencies.
7) Splenectomy.
8) Any preexisting medical condition requiring chronic systemic steroid
or immunosuppressive therapy (steroids for the treatment of radiation
pneumonitis are allowed).
9) Receipt of immunotherapy (as defined in the protocol) within 4 weeks
prior to randomization.
10) Receipt of investigational systemic drugs (including off-label use of
approved products) within 4 weeks (28 days) prior to randomization.
11) Autoimmune disease.
12) Active or chronic infectious hepatitis.
13) Infectious process that, in the opinion of the investigator, could compromise the subject's ability to mount an immune response.
14) Clinically significant hepatic dysfunction, renal dysfunction and
cardiac disease as defined in the protocol.
15) Clinically significant hepatic dysfunction, renal dysfunction and
cardiac disease as defined in the protocol.
16) Clinically significant cardiac disease, e.g., New York Heart
Association (NYHA) classes III-IV; uncontrolled angina, uncontrolled
arrhythmia or
uncontrolled hypertension, myocardial infarction in the previous 6
months as confirmed by an ECG.
17) Pregnant or breast-feeding women (for details see
Inclusion Criteria).
18) Known drug abuse/alcohol abuse.
19) Participation in another interventional clinical trial within the past
28 days (excluding purely observational studies).
20) Requires concurrent treatment with a non-permitted drug.
21) Known hypersensitivity to any of the trial treatment ingredients.
22) Legal incapacity or limited legal capacity.
23) Any other reason that, in the opinion of the investigator, precludes
the subject from participating in the trial |
• Precedente terapia specifica per il carcinoma polmonare (chirurgia compresa) diversa dalla CRT concomitante iniziale.
• Chemioterapia concomitante alla radioterapia ricevuta a dosaggi solamente radiosensibilizzanti
• Malattia metastatica.
• Effusione pleurica maligna alla diagnosi iniziale, durante la CRT iniziale e/o all’ingresso nello studio.
• Anamnesi attuale o precedente di neoplasia diversa dal carcinoma polmonare, ad eccezione dei tumori cutanei non melanomatosi trattati terapeuticamente, del carcinoma in situ della cervice o di altro tumore trattato terapeuticamente e senza evidenza di malattia per almeno 5 anni.
• Un’immunodeficienza accertata, comprese l’infezione da virus dell’immunodeficienza umana (HIV) e altre immunodeficienze cellulari, l’ipogammaglobulinemia o la disgammaglobulinemia; soggetti che presentano immunodeficienze ereditarie, congenite o acquisite.
• Splenectomia.
• Qualsiasi condizione medica preesistente che richieda una terapia steroidea cronica sistemica o immunosoppressiva (gli steroidi per il trattamento della polmonite da radiazione sono ammessi).
• Immunoterapia (come definito da protocollo) nelle 4 settimane (28 giorni) precedenti alla randomizzazione.
• Farmaci sperimentali sistemici (compreso l’uso off-label di prodotti approvati) ricevuti nelle 4 settimane (28 giorni) precedenti alla randomizzazione.
• Malattia autoimmune.
• Epatite infettiva attiva o cronica.
• Processo infettivo che, a giudizio dello sperimentatore, potrebbe compromettere la capacità del soggetto di produrre una risposta immunitaria.
• Disfunzione epatica clinicamente significativa, disfunzione renale clinicamente significativa e malattia cardiaca clinicamente significativa come da protocollo, ad es., classi III-IV della classificazione NYHA (New York Heart Association), angina incontrollata, aritmia incontrollata o ipertensione incontrollata, infarto miocardico nei 6 mesi precedenti come confermato da un ECG.
• Donne in stato di gravidanza o allattamento (per dettagli, vedasi i Criteri di inclusione).
• Abuso accertato di alcool/droghe.
• Partecipazione a un altro studio clinico interventistico negli ultimi 28 giorni (esclusi gli studi puramente osservazionali).
• Necessità di un trattamento concomitante con un farmaco non consentito.
• Accertata ipersensibilità ad uno qualsiasi dei componenti del trattamento in studio.
• Incapacità legale assoluta o relativa.
• Qualsiasi altro motivo che, a giudizio dello sperimentatore, precluda la partecipazione del soggetto allo studio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall Survival (OS) time. OS time will be measured from the date of
randomization to the date of death or up to 5 years, whichever is first. |
tempo di sopravvivenza complessiva (overall survival, OS). L’OS sarà misurato dalla data di randomizzazione alla data del decesso o fino a 5 anni, a seconda di cosa si verifica prima |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to 5 years or date of death, whichever is first |
dopo 5 anni o alla data di decesso, a seconda di cosa si verifica prima |
|
E.5.2 | Secondary end point(s) |
- TTSP as measured by the LCSS.
- PFS time as determined by the investigator.
- TTP as determined by the investigator.
- Number of Subjects With Adverse Events (AEs), Serious AEs, treatment
emergent AEs, AEs leading to death, and AEs with National Cancer
Institute-Common Toxicity Criteria (NCI−CTC) toxicity Grade 3 or 4 and
Injection site reactions (ISRs)
- Number of subjects with clinically significant abnormal
Electrocardiogram (ECG) and lab parameters |
• TTSP come misurato mediante LCSS
• PFS come determinato dallo sperimentatore
• TTP come determinato dallo sperimentatore
• Numero di soggetti con eventi avversi (EA), eventi avversi gravi, eventi avversi emergenti dal trattamento, eventi avversi che portano alla morte, e AES di tossicità di grado 3 o 4 secondo criteri di tossicità comune del National Cancer Institute (NCI-CTC) e Reazioni nel sito di iniezione (ISR)
• Numero di soggetti con elettrocardiogramma (ECG) anormale e parametri di laboratorio clinicamente significativi |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline up to 12 weeks after the last dose administration |
al basale fino a 12 settimane dopo l'ultima dose somministrata |
|
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 | 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 | 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) | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 93 |
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 |
Belgium |
Canada |
Denmark |
France |
Ireland |
Italy |
Austria |
Netherlands |
New Zealand |
Portugal |
Slovakia |
Sweden |
Australia |
Belarus |
Chile |
Czech Republic |
Germany |
Saudi Arabia |
Spain |
Kuwait |
Mexico |
Oman |
Poland |
Qatar |
Russian Federation |
South Africa |
Switzerland |
Turkey |
United Arab Emirates |
United Kingdom |
United States |
|
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
|
Previous trial experience with tecemotide shows that subjects have
remained on trial treatment for long periods of time. Therefore, the end
of trial is defined as the date that the last eligible subject is transferred
to an extension protocol or continues tecemotide treatment in another
appropriate setting. |
Da precedenti studi con tecemotide è stato dimostrato che i soggetti sono
rimasti in trattamento per lunghi periodi di tempo. Pertanto, la conclusione della sperimentazione viene definita come la data in cui l'ultimo soggetto elegibile viene trasferito ad un protocollo di estensione o continua il trattamento con tecemotide in un'altra modalità appropriata
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
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 |