E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC) not eligible for curative treatment |
lokal fortgeschrittenes oder metastasiertes großzellig-neuroendokrines Lungenkarzinom (LCNEC), nicht für eine kurative Behandlung geeignet |
|
E.1.1.1 | Medical condition in easily understood language |
locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung not eligible for curative treatment |
|
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 | LLT |
E.1.2 | Classification code | 10078184 |
E.1.2 | Term | Neuroendocrine tumor of the lung metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10078175 |
E.1.2 | Term | Neuroendocrine tumour of the lung metastatic |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC. |
Wirksamkeit von Atezolizumab zusätzlich zur Standard-Chemotherapie (Platinum/Etoposid) in LCNEC. |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety, tolerability and efficacy of Atezolizumab in addition to standard of care (SoC; Platinum/Etoposide) in LCNEC. |
Sicherheit, Verträglicheit und Wirksamkeit von Atezolizumab zusätzlich zur Standard-Chemotherapie (Platinum/Etoposid) in LCNEC. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Written informed consent 2) Patients with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung (LCNEC) without curative treatment options (patients with mixed histology are eligible if LCNEC is the predominant histology i.e. ≥50%) 3) Previously untreated with systemic therapy (note: patients relapsing after curative radio chemotherapy or adjuvant chemotherapy are eligible if relapse occurs ≥6 months after discontinuation of curative treatment) 4) Planned treatment with Carboplatin or Cisplatin and Etoposide (SoC) 5) ECOG performance status: 0-2 6) age ≥18 years 7) measurable disease according to RECIST v1.1 8) adequate organ function defined as: - ALAT/ASAT ≤2.5x ULN or ≤3.5x ULN in case of liver metastases - Bilirubin ≤1.5x ULN or ≤2.5x ULN in case of liver metastases - Creatinine ≤1.5x ULN or Creatinine clearance according to Cockroft-Gault >60 ml/min - Neutrophils ≥1 Gpt/l, Platelets >50 Gpt/l unless caused by bone marrow carcinosis
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1) Schriftliche Zustimmung zur Studienteilnahme (Patienteninformation) 2) Patienten mit lokal fortgeschrittenem oder metastasiertem großzellig-neuroendokrinem Lungenkarzinom (LCNEC), die nicht für eine kurative Behandlung geeignet sind (Patienten mit gemischter Histologie sind geeignet, wenn LCNEC die vorscherrschende Histologie ≥50% ist) 3) Keine Vorbehandlung mit systemischer Therapie (Hinweis: Patienten mit Rezidiv nach kurativer Radiochemotherapie oder adjuvanter Chemotherapie sind geeignet, wenn das Rezidiv ≥6 Monate nach Beendigung der kurativen Therapie auftrat) 4) Geplante Behandlung mit Carboplatin oder Cisplatin und Etoposid (Standard-Chemotherapie) 5) ECOG Status: 0-2 6) Alter ≥18 Jahre 7) messbare Erkrankung gemäß RECIST v1.1 8) adäquate Organfunktionen definiert als: - ALAT/ASAT ≤2.5x ULN oder ≤3.5x ULN im Fall von Lebermetastasen - Bilirubin ≤1.5x ULN oder ≤2.5x ULN im Fall von Lebermetastasen - Kreatinin ≤1.5x ULN oder Kreatinin Clearance gemäß Cockroft-Gault >60 ml/min - Neutrophile ≥1 Gpt/l, Thrombozyten >50 Gpt/l solange nicht durch Knochenmark-Karzinose verursacht |
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E.4 | Principal exclusion criteria |
1) Symptomatic brain metastases (patients with asymptomatic brain metastases are allowed provided they are stable without steroid treatment for at least 3 weeks) 2) Severe autoimmune disease (patients with endocrine autoimmune disorders are allowed as long as they are on stable substitution treatment) 3) Severe uncontrolled infection 4) Prior treatment with either Atezolizumab or other immune checkpoint inhibitor 5) Any prior treatment for metastatic disease
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1) Symptomatische Hirnmetastasen (Patienten mit asymptomatischen Hirnmetastasen sind erlaubt, wenn sie für mindestens 3 Wochen ohne Steroidbehandlung stabil sind) 2) schwere Autoimmun-Erkrankungen (Patienten mit endokrinen Autoimmun-Erkrankungen sind erlaubt, solange sie in stabiler Substitutions-Behandlung sind) 3) schwere unkontrollierte Infektion 4) vorherige Behandlung mit entweder Atezolizumab oder einem anderen Immuncheckpoint-Inhibitor 5) jedwede vorherige systemische Behandlung der metastasierten Erkrankung |
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E.5 End points |
E.5.1 | Primary end point(s) |
overall survival (OS) |
Gesamtüberleben |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
time to event endpoint |
Time-to-Event Endpunkt (bei Eintreten des Ereignisses) |
|
E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints (ORR, iORR, DCR, PFS, iPFS, DoR, PFS rate at one year, iPFS rate at one year, OS rate at one year), Safety: Incidence, nature, causality, seriousness and severity of adverse events using NCI CTCAE (v5.0) |
sekundäre Wirksamkeits-Endpunkte (ORR, iORR, DCR, PFS, iPFS, DoR, PFS 1-Jahres-Rate, iPFS 1-Jahres-Rate, OS 1-Jahres-Rate), Sicherheit: Inzidenz, Art, Kausalzusammenhang, Bedeutung und Schweregrad von unerwünschten Ereignissen gemäß NCI CTCAE Klassifizierung (v5.0) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during whole study and time to event endpoints |
während der gesamten Studie und bei Eintreten des Ereignisses |
|
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 15 |
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 | No |
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
|
LVLS ( last visit of the last subject)
|
letzte Visite des letzten Patienten |
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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 | |
E.8.9.1 | In the Member State concerned months | 72 |
E.8.9.1 | In the Member State concerned days | |