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A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung (LCNEC-ALPINE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05470595
Recruitment Status : Recruiting
First Posted : July 22, 2022
Last Update Posted : July 22, 2022
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Technische Universität Dresden

Brief Summary:
This phase II clinical trial evaluates the efficacy, safety and tolerability of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC.

Condition or disease Intervention/treatment Phase
Large Cell Neuroendocrine Carcinoma of the Lung Drug: Atezolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 67 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
Actual Study Start Date : January 18, 2022
Estimated Primary Completion Date : January 31, 2028
Estimated Study Completion Date : January 31, 2029


Arm Intervention/treatment
Experimental: Atezolizumab/Platinum/Etoposide
Atezolizumab/Platinum/Etoposide Platinum will be cisplatin or carboplatin at the investigators discretion.
Drug: Atezolizumab
Atezolizumab (IMP) will be added to Platinum/Etoposide (Standard-of-Care). Four cycles of combined immunochemotherapy 3qw will be follows by maintenance with atezolizumab monotherapy until progression.




Primary Outcome Measures :
  1. Overall survival [ Time Frame: appr. 72 months ]
    To assess the efficacy of Atezolizumab in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC as measured by overall survival.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: appr. 72 months ]
    According to RECIST v1.1 as assessed by local investigator.

  2. Immune Objective Response Rate (iORR) [ Time Frame: appr. 72 months ]
    According to iRECIST as assessed by local investigator.

  3. Disease Control Rate (DCR) [ Time Frame: appr. 72 months ]
    According to RECIST v1.1 as assessed by local investigator.

  4. Progression Free Survival (PFS) [ Time Frame: appr. 72 months ]
  5. Immune Progression Free Survival (iPFS) [ Time Frame: appr. 72 months ]
  6. Duration of Response (DoR) [ Time Frame: appr. 72 months ]
  7. Progression Free Survival (PFS) rate at one year [ Time Frame: 1 year ]
  8. Immune Progression Free Survival (iPFS) rate at one year [ Time Frame: 1 year ]
  9. Overall survival at one year [ Time Frame: 1 year ]
  10. Incidence, intensity, seriousness, relationship to Atezolizumab, and outcome of adverse events graded according to NCI CTCAE (v5.0). [ Time Frame: appr. 72 months ]

Other Outcome Measures:
  1. Secondary efficacy endpoints in defined molecular subtypes (NSCLC-type / SCLC-type) [ Time Frame: appr. 72 months ]
  2. Quality of Life assessed by EORTC QLQ-C30. [ Time Frame: appr. 72 months ]
  3. Quality of Life assessed by EORTC QLQ-LC13. [ Time Frame: appr. 72 months ]
  4. Immune Effectors [ Time Frame: appr. 72 months ]
    Changes in cellular and humoral immune effectors in peripheral blood and their correlation with response.

  5. Mutational Landscape [ Time Frame: appr. 72 months ]
    Mutational landscape of LCNEC in comparison to SCLC as well as squamous and Adenocarcinoma of the lung. The analysis will be using whole genome sequencing.

  6. Tumor DNA (tDNA) level [ Time Frame: appr. 72 months ]
    Dynamics of circulating tumor DNA levels (changes from baseline).

  7. Therapy Resistance [ Time Frame: appr. 72 months ]
    Mechanisms of therapy resistance (changes of immune invasion and mutational landscape in tumor re-biopsy upon progression).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    1. ALAT/ASAT ≤2.5x ULN or ≤3.5x ULN in case of liver metastases
    2. Bilirubin ≤1.5x ULN or ≤2.5x ULN in case of liver metastases
    3. Creatinine ≤1.5x ULN or Creatinine clearance according to Cockroft-Gault >60 ml/min
    4. Neutrophils ≥1 Gpt/l, Platelets >50 Gpt/l unless caused by bone marrow carcinosis

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05470595


Contacts
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Contact: Martin Wermke, MD +49 351 7566 martin.wermke@ukdd.de
Contact: Felix C Saalfeld, MD felix.saalfeld@ukdd.de

Locations
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Germany
Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik Not yet recruiting
Berlin, Germany, 10117
Contact: Nikolaj Frost, MD         
Evangelische Lungenklinik Recruiting
Berlin, Germany, 12125
Contact: Christian Grohé, Prof. Dr.         
Universitätsklinikum Dresden, Medizinische Klinik 1 Recruiting
Dresden, Germany, 01307
Contact: Martin Wermke, MD         
Klinikum der J.W. Goethe Universität, Medizinische Klinik II Not yet recruiting
Frankfurt am Main, Germany, 60590
Contact: Jan Alexander Stratmann, MD         
Asklepios Fachkliniken München-Gauting Recruiting
Gauting, Germany, 82131
Contact: Niels Reinmuth, MD         
LungenClinic Grosshansdorf GmbH Recruiting
Großhansdorf, Germany, 22927
Contact: Martin Reck, MD         
Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg Not yet recruiting
Heidelberg, Germany, 69126
Contact: Farastuk Bozorgmehr, MD         
Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH Not yet recruiting
Hemer, Germany, 58675
Contact: Monika Serke, MD         
Lungenfachklinik Immenhausen Recruiting
Immenhausen, Germany, 34376
Contact: Achim Rittmeyer, MD         
Klinikum der Universität zu Köln, Klinik I für Innere Medizin Not yet recruiting
Köln, Germany, 50937
Contact: Jürgen Wolf, MD         
Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik Not yet recruiting
Mainz, Germany, 55131
Contact: Jürgen Alt, MD         
Pius Hospital, Klinik für Hämatologie und Onkologie Recruiting
Oldenburg, Germany, 26121
Contact: Frank Griesinger, MD         
Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin Not yet recruiting
Winnenden, Germany, 71364
Contact: Maria Netchaeva         
Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken Not yet recruiting
Würzburg, Germany, 97078
Contact: Pius Jung, MD         
Sponsors and Collaborators
Technische Universität Dresden
Roche Pharma AG
Investigators
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Principal Investigator: Martin Wermke, MD Technische Universität Dresden (TUD)
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Responsible Party: Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT05470595    
Other Study ID Numbers: TUD-ALPINE-077
2020-002683-31 ( EudraCT Number )
First Posted: July 22, 2022    Key Record Dates
Last Update Posted: July 22, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Technische Universität Dresden:
Lung Cancer
LCNEC
Neuroendocrine Carcinoma
Additional relevant MeSH terms:
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Carcinoma, Neuroendocrine
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Atezolizumab
Antineoplastic Agents