Einleitung wieder einblenden
NCT03133546 | SNCTP000002426

Eine Forschungsstudie, welche die Kombination aus Osimertinib und Bevacizumab im Vergleich zu Osimertinib allein bei Patienten mit fortgeschrittenem "nicht-kleinzelligem Lungenkarzinom“ (NSCLC) untersucht, deren Krebserkrankung spezifische Genmutationen des epidermalen Wachstumsfaktor-Rezeptors (EGFR) aufweist und sich unter der bisherigen Behandlung verschlimmert hat.

Datenbasis: BASEC (Import vom 22.01.2018), WHO (Import vom 21.01.2018)
Geändert: 14.01.2018
Krankheitskategorie: Lungenkrebs

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

Osimertinib (Tagrisso®) ist ein neuer, so genannter selektiver Tyrosinkinase-Inhibitor TKI der dritten Generation. Forschungsstudien mit Osimertinib bei Patienten mit nicht-kleinzelligem Lungenkarzinom und den spezifischen Genmutationen haben vielversprechende Ergebnisse gezeigt.
Bevacizumab (Avastin®) ist ein Antikörper, der das Wachstum der den Tumor versorgenden Blutgefässe hemmt.

Ziel dieser aktuellen Studie ist es, die Wirksamkeit (wie gut die Behandlung funktioniert) und die Verträglichkeit (ob Nebenwirkungen auftreten) der Kombination aus Osimertinib und Bevacizumab im Vergleich zu Osimertinib allein bei Patienten mit fortgeschrittenem NSCLC mit EGFR-Mutationen zu untersuchen, deren Erkrankung unter Standardbehandlung mit TKI fortschreitet.

Sowohl Osimertinib als auch Bevacizumab sind vom Schweizerischen Heilmittelinstitut Swissmedic als auch von der Europäischen Arzneimittelagentur für die Behandlung von NSCLC zugelassen. Die kombinierte Anwendung der beiden Arzneimittel wird in dieser Studie untersucht.

Untersuchte Krankheiten (Datenquelle: BASEC)

Eine Art von Lungenkrebs, welche als „nicht-kleinzelliges Lungenkarzinom“ (non-small cell lung cancer, NSCLC) bezeichnet wird und spezifische Genmutationen (Veränderungen des Erbguts) des epidermalen Wachstumsfaktor-Rezeptors (epithelial growth factor receptor, EGFR) aufweist. Die Lungenkrebserkrankung hat sich während der Behandlung mit der bisherigen Standardtherapie aus Tyrosinkinase-Inhibitoren (TKI) verschlimmert oder sich auf andere Bereiche des Körpers ausgebreitet (Metastasierung).

Health conditions (Datenquelle: WHO)

Non Small Cell Lung Cancer Metastatic;Non Small Cell Lung Cancer Metastatic;Non Small Cell Lung Cancer Metastatic;Non Small Cell Lung Cancer Metastatic

Seltene Krankheit (Datenquelle: BASEC)

Nein

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

• Osimertinib: 80 mg oral, täglich
ODER
• Osimertinib: 80 mg oral, täglich PLUS Bevacizumab: 15 mg/kg intravenöse Injektion an Tag 1 jedes 3-wöchigen Zyklus.

Interventions (Datenquelle: WHO)

Drug: Osimertinib;Drug: Bevacizumab;Drug: Osimertinib;Drug: Bevacizumab;Drug: Osimertinib;Drug: Bevacizumab;Drug: Osimertinib;Drug: Bevacizumab

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

- Nicht-kleinzelliges Lungenkarzinom (NSCLC) im Stadium IIIb - IVb, fortschreitend nach vorangehender TKI Therapie (Erlotinib, Gefitinib, Dacomitinib oder Afatinib).
- Histologische oder zytologische Bestätigung der EGFR Mutation (Exon 19 Deletion oder Exon 21 L858R).
- Lokal bestätigte T790M Mutation

Ausschlusskriterien (Datenquelle: BASEC)

- Patienten mit gemischtem Nicht-kleinzelligem Lungenkarzinom (NSCLC) mit vorherrschendem Plattenepithelkarzinom oder mit irgendeinem Komponenten des Kleinzelligem Lungenkarzinoms (SCLC)
- Symptomatische oder aktive Metastasen im Zentralnervensystem
- Patienten welche zur Zeit Medikamente oder pflanzliche Nahrungsergänzungsmittel einnehmen, die als Induktoren des CYP3A4 Enzyms bekannt sind.

Inclusion/Exclusion Criteria (Datenquelle: WHO)


Inclusion Criteria:

- Patients (male/female) must be >18 years of age.

- Patients diagnosed with NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or
IVa/IVb according to 8th TNM classification, after progression following prior EGFR
TKI therapy (erlotinib, gefitinib, dacomitinib or afatinib) as the most recent
treatment regimen;

- Pathological diagnosis of predominantly non-squamous NSCLC;

- Maximum one line of previous platinum based chemotherapy;

- Histological or cytological confirmation of EGFRm (exon 19 deletion or exon 21L858R);

- Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating
tumour DNA, documented in tissue, plasma or serum after disease progression on the
most recent treatment regimen;

- Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE
tumor material is not yet fully depleted) after disease progression on the most recent
EGFR TKI treatment available for central confirmation of T790M;

- Measurable or evaluable disease according to RECIST 1.1;

- Adequate haematological, renal and liver function;

- World Health Organization (WHO) performance status 0-2.

Exclusion Criteria:

- Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small
cell lung cancer (SCLC) component;

- Symptomatic or active central nervous system metastases, as indicated by progressive
growth or increasing need of steroids.

- Patients currently receiving medications or herbal supplements known to be potent
CYP3A4 inducers;

- Patients with any unresolved toxicities from prior therapy greater than CTCAE V 4.0
grade 1 (exception: alopecia & grade 2, prior platinuma-therapy related neuropathy)

- Previous treatment with osimertinib and/or bevacizumab;
;
Inclusion Criteria:

- Patients (male/female) must be >18 years of age.

- Patients diagnosed with NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or
IVa/IVb according to 8th TNM classification, after progression following prior EGFR
TKI therapy (erlotinib, gefitinib, dacomitinib or afatinib) as the most recent
treatment regimen;

- Pathological diagnosis of predominantly non-squamous NSCLC;

- Maximum one line of previous platinum based chemotherapy;

- Histological or cytological confirmation of EGFRm (exon 19 deletion or exon 21L858R);

- Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating
tumour DNA, documented in tissue, plasma or serum after disease progression on the
most recent treatment regimen;

- Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE
tumor material is not yet fully depleted) after disease progression on the most recent
EGFR TKI treatment available for central confirmation of T790M;

- Measurable or evaluable disease according to RECIST 1.1;

- Adequate haematological, renal and liver function;

- World Health Organization (WHO) performance status 0-2.

Exclusion Criteria:

- Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small
cell lung cancer (SCLC) component;

- Symptomatic or active central nervous system metastases, as indicated by progressive
growth or increasing need of steroids.

- Patients currently receiving medications or herbal supplements known to be potent
CYP3A4 inducers;

- Patients with any unresolved toxicities from prior therapy greater than CTCAE V 4.0
grade 1 (exception: alopecia & grade 2, prior platinuma-therapy related neuropathy)

- Previous treatment with osimertinib and/or bevacizumab;
;
Inclusion Criteria:

- Patients (male/female) must be >18 years of age.

- Patients diagnosed with NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or
IVa/IVb according to 8th TNM classification, after progression following prior EGFR
TKI therapy (erlotinib, gefitinib, dacomitinib or afatinib) as the most recent
treatment regimen;

- Pathological diagnosis of predominantly non-squamous NSCLC;

- Maximum one line of previous platinum based chemotherapy;

- Histological or cytological confirmation of EGFRm (exon 19 deletion or exon 21L858R);

- Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating
tumour DNA, documented in tissue, plasma or serum after disease progression on the
most recent treatment regimen;

- Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE
tumor material is not yet fully depleted) after disease progression on the most recent
EGFR TKI treatment available for central confirmation of T790M;

- Measurable or evaluable disease according to RECIST 1.1;

- Adequate haematological, renal and liver function;

- World Health Organization (WHO) performance status 0-2.

Exclusion Criteria:

- Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small
cell lung cancer (SCLC) component;

- Symptomatic or active central nervous system metastases, as indicated by progressive
growth or increasing need of steroids.

- Patients currently receiving medications or herbal supplements known to be potent
CYP3A4 inducers;

- Patients with any unresolved toxicities from prior therapy greater than CTCAE V 4.0
grade 1 (exception: alopecia & grade 2, prior platinuma-therapy related neuropathy)

- Previous treatment with osimertinib and/or bevacizumab;
;
Inclusion Criteria:

- Patients (male/female) must be >18 years of age.

- Patients diagnosed with NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or
IVa/IVb according to 8th TNM classification, after progression following prior EGFR
TKI therapy (erlotinib, gefitinib, dacomitinib or afatinib) as the most recent
treatment regimen;

- Pathological diagnosis of predominantly non-squamous NSCLC;

- Maximum one line of previous platinum based chemotherapy;

- Histological or cytological confirmation of EGFRm (exon 19 deletion or exon 21L858R);

- Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating
tumour DNA, documented in tissue, plasma or serum after disease progression on the
most recent treatment regimen;

- Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE
tumor material is not yet fully depleted) after disease progression on the most recent
EGFR TKI treatment available for central confirmation of T790M;

- Measurable or evaluable disease according to RECIST 1.1;

- Adequate haematological, renal and liver function;

- World Health Organization (WHO) performance status 0-2.

Exclusion Criteria:

- Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small
cell lung cancer (SCLC) component;

- Symptomatic or active central nervous system metastases, as indicated by progressive
growth or increasing need of steroids.

- Patients currently receiving medications or herbal supplements known to be potent
CYP3A4 inducers;

- Patients with any unresolved toxicities from prior therapy greater than CTCAE V 4.0
grade 1 (exception: alopecia & grade 2, prior platinuma-therapy related neuropathy)

- Previous treatment with osimertinib and/or bevacizumab;

Weitere Angaben zur Studie im WHO-Primärregister

https://clinicaltrials.gov/show/NCT03133546

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03133546

Weitere Informationen zur Studie

Registrationsdatum der Studie

20.04.2017

Einschluss der ersten teilnehmenden Person

31.05.2017

Rekrutierungsstatus

Recruiting

Wissenschaftlicher Titel (Datenquelle: WHO)

A Randomised Phase II Trial of Osimertinib and Bevacizumab Versus Osimertinib Alone as Second-line Treatment in Stage IIIb-IVb NSCLC With Confirmed EGFRm and T790M

Studientyp (Datenquelle: WHO)

Interventional

Design der Studie (Datenquelle: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Datenquelle: WHO)

Phase 2

Primäre Endpunkte (Datenquelle: WHO)

Progression Free Survival (PFS);Progression Free Survival (PFS);Progression Free Survival (PFS);Progression Free Survival (PFS)

Sekundäre Endpunkte (Datenquelle: WHO)

Objective Response Rate (ORR);Disease Control;Adverse Events;Overall Survival (OS)

Kontakt für Auskünfte (Datenquelle: WHO)

Please refer to primary and secondary sponsors

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Lausanne, St Gallen, Winterthur, Zürich

Durchführungsländer (Datenquelle: WHO)

Ireland, Korea, Netherlands, Republic of, Singapore, Spain, Switzerland

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Barbara Ruepp
+41 31 511 94 16
regulatoryoffice@etop-eu.org

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD;Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD;Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD;Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD
Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;;Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;;Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;;Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;
;;+41315119416;;;+41315119416;;;+41315119416;;;+41315119416
;;regulatoryoffice@etop-eu.org;;;regulatoryoffice@etop-eu.org;;;regulatoryoffice@etop-eu.org;;;regulatoryoffice@etop-eu.org

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD;Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD;Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD;Solange Peters, MD;Rolf Stahel, MD;Barbara Ruepp, PharmD
Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;;Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;;Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;;Centre Hospitalier Universitaire Vaudois;University Hospital Zuerich, Zurich, Switzerland;
;;+41315119416;;;+41315119416;;;+41315119416;;;+41315119416
;;regulatoryoffice@etop-eu.org;;;regulatoryoffice@etop-eu.org;;;regulatoryoffice@etop-eu.org;;;regulatoryoffice@etop-eu.org

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

European Thoracic Oncology Platform

Weitere Sponsoren (Datenquelle : WHO)

AstraZeneca;Hoffmann-La Roche

Weitere Studienidentifikationsnummern

BASEC ID (Datenquelle: BASEC)

2017-00106

Secondary ID (Datenquelle: WHO)

2016-002029-12;ESR-15-11666;MO39447;ETOP 10-16