Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial.


Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
24 Sep 2022
Historique:
received: 08 02 2022
accepted: 09 09 2022
entrez: 24 9 2022
pubmed: 25 9 2022
medline: 28 9 2022
Statut: epublish

Résumé

Recently, the combination of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab with first-line chemotherapy has demonstrated to improve outcome for patients with advanced small cell lung cancer (SCLC), leading to approval of this regimen. At the same time, accumulating (pre-)clinical data suggest synergisms of radiotherapy and immunotherapy via the radiation-mediated induction of anti-tumor immunogenicity. Combining the recent findings, the TREASURE trial aims at further enhancing response to upfront chemo-immunotherapy by the addition of thoracic radiotherapy (TRT). The TREASURE trial is a randomized, multicenter, phase II clinical trial ( ClinicalTrials.gov identifier, NCT04462276). One hundred four patients suffering from extensive disease (ED) SCLC, with any response to the standard of care induction chemo-immunotherapy will be randomized to receive atezolizumab maintenance therapy with or without TRT. The primary endpoint of this study is overall survival (OS). Secondary endpoints include further measures of efficacy, safety, and the collection of biomarker samples. A safety interim analysis will take place after n = 23 patients receiving TRT have been observed for three months after the end of TRT. This trial will investigate whether treatment efficacy can be improved by adding TRT to atezolizumab maintenance therapy in ED SCLC patients with any response after chemo-immunotherapy. Safety and feasibility of such a regimen will be evaluated, and biomaterials for a translational research project will be collected. Together, the results of this trial will deepen our comprehension of how checkpoint inhibition and radiotherapy interact and contribute to the evolving landscape of SCLC therapy. Clinicaltrials.gov identifier: NCT04462276 (Date of initial registration: 8th July 2020), https://clinicaltrials.gov/ct2/show/NCT04462276 Eudra-CT Number: 2019-003916-29 (Date of initial registration: 30th March 2020), https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003916-29/DE.

Sections du résumé

BACKGROUND BACKGROUND
Recently, the combination of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab with first-line chemotherapy has demonstrated to improve outcome for patients with advanced small cell lung cancer (SCLC), leading to approval of this regimen. At the same time, accumulating (pre-)clinical data suggest synergisms of radiotherapy and immunotherapy via the radiation-mediated induction of anti-tumor immunogenicity. Combining the recent findings, the TREASURE trial aims at further enhancing response to upfront chemo-immunotherapy by the addition of thoracic radiotherapy (TRT).
METHODS/DESIGN METHODS
The TREASURE trial is a randomized, multicenter, phase II clinical trial ( ClinicalTrials.gov identifier, NCT04462276). One hundred four patients suffering from extensive disease (ED) SCLC, with any response to the standard of care induction chemo-immunotherapy will be randomized to receive atezolizumab maintenance therapy with or without TRT. The primary endpoint of this study is overall survival (OS). Secondary endpoints include further measures of efficacy, safety, and the collection of biomarker samples. A safety interim analysis will take place after n = 23 patients receiving TRT have been observed for three months after the end of TRT.
DISCUSSION CONCLUSIONS
This trial will investigate whether treatment efficacy can be improved by adding TRT to atezolizumab maintenance therapy in ED SCLC patients with any response after chemo-immunotherapy. Safety and feasibility of such a regimen will be evaluated, and biomaterials for a translational research project will be collected. Together, the results of this trial will deepen our comprehension of how checkpoint inhibition and radiotherapy interact and contribute to the evolving landscape of SCLC therapy.
TRIAL REGISTRATION BACKGROUND
Clinicaltrials.gov identifier: NCT04462276 (Date of initial registration: 8th July 2020), https://clinicaltrials.gov/ct2/show/NCT04462276 Eudra-CT Number: 2019-003916-29 (Date of initial registration: 30th March 2020), https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003916-29/DE.

Identifiants

pubmed: 36153496
doi: 10.1186/s12885-022-10074-9
pii: 10.1186/s12885-022-10074-9
pmc: PMC9509547
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
B7-H1 Antigen 0
Biocompatible Materials 0
atezolizumab 52CMI0WC3Y

Banques de données

ClinicalTrials.gov
['NCT04462276']

Types de publication

Clinical Trial Protocol Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1011

Informations de copyright

© 2022. The Author(s).

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Auteurs

Farastuk Bozorgmehr (F)

Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany. Farastuk.Bozorgmehr@med.uni-heidelberg.de.
Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany. Farastuk.Bozorgmehr@med.uni-heidelberg.de.

Petros Christopoulos (P)

Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.

Inn Chung (I)

Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.

Jelena Cvetkovic (J)

Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.

Manuel Feißt (M)

University Hospital of Heidelberg, Institute of Medical Biometry, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.

Johannes Krisam (J)

University Hospital of Heidelberg, Institute of Medical Biometry, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.

Marc A Schneider (MA)

Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.
Thoraxklinik at University Hospital of Heidelberg, Translational Research Unit (STF), Röntgenstraße 1, 69126, Heidelberg, Germany.

Claus Peter Heußel (CP)

Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.
Thoraxklinik at University Hospital of Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Röntgenstraße 1, 69126, Heidelberg, Germany.

Michael Kreuter (M)

Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.
Thoraxklinik at University Hospital of Heidelberg, Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Röntgenstraße 1, 69126, Heidelberg, Germany.

Daniel W Müller (DW)

Institute of Clinical Cancer Research IKF GmbH at Northwest Hospital, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany.

Michael Thomas (M)

Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany.
Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.

Stefan Rieken (S)

Department of Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

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Classifications MeSH