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History of Changes for Study: NCT05470595
A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung (LCNEC-ALPINE)
Latest version (submitted November 1, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 20, 2022 None (earliest Version on record)
2 November 1, 2023 Study Status
Comparison Format:
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Study NCT05470595
Submitted Date:  July 20, 2022 (v1)
Open or close this module Study Identification
Unique Protocol ID: TUD-ALPINE-077
Brief Title: A Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung (LCNEC-ALPINE)
Official Title: A Phase II, Single-arm Trial of Atezolizumab/Platinum/Etoposide for the Treatment of Advanced Large-cell Neuroendocrine Cancer of the Lung
Secondary IDs: 2020-002683-31 [EudraCT Number]
Open or close this module Study Status
Record Verification: July 2022
Overall Status: Recruiting
Study Start: January 18, 2022
Primary Completion: January 31, 2028 [Anticipated]
Study Completion: January 31, 2029 [Anticipated]
First Submitted: July 13, 2022
First Submitted that
Met QC Criteria:		 July 20, 2022
First Posted: July 22, 2022 [Actual]
Last Update Submitted that
Met QC Criteria:		 July 20, 2022
Last Update Posted: July 22, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Technische Universität Dresden
Responsible Party: Sponsor
Collaborators: Roche Pharma AG
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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.
Detailed Description:
Open or close this module Conditions
Conditions: Large Cell Neuroendocrine Carcinoma of the Lung
Keywords: Lung Cancer
LCNEC
Neuroendocrine Carcinoma
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 67 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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.
Open or close this module Outcome Measures
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).
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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
Open or close this module Contacts/Locations
Central Contact Person: Martin Wermke, MD
Telephone: +49 351 7566
Email: martin.wermke@ukdd.de
Central Contact Backup: Felix C Saalfeld, MD
Email: felix.saalfeld@ukdd.de
Study Officials: Martin Wermke, MD
Principal Investigator
Technische Universität Dresden (TUD)
Locations: Germany
Charité - Universitätsklinikum Berlin Centrum 12, Medizinische Klinik
[Not yet recruiting]
Berlin, Germany, 10117
Contact:Contact: Nikolaj Frost, MD
Evangelische Lungenklinik
[Recruiting]
Berlin, Germany, 12125
Contact:Contact: Christian Grohé, Prof. Dr.
Universitätsklinikum Dresden, Medizinische Klinik 1
[Recruiting]
Dresden, Germany, 01307
Contact:Contact: Martin Wermke, MD
Klinikum der J.W. Goethe Universität, Medizinische Klinik II
[Not yet recruiting]
Frankfurt am Main, Germany, 60590
Contact:Contact: Jan Alexander Stratmann, MD
Asklepios Fachkliniken München-Gauting
[Recruiting]
Gauting, Germany, 82131
Contact:Contact: Niels Reinmuth, MD
LungenClinic Grosshansdorf GmbH
[Recruiting]
Großhansdorf, Germany, 22927
Contact:Contact: Martin Reck, MD
Thoraxklinik Heidelberg gGmbH, Universitätsklinikum Heidelberg
[Not yet recruiting]
Heidelberg, Germany, 69126
Contact:Contact: Farastuk Bozorgmehr, MD
Lungenklinik Hemer des Deutschen Gemeinschafts-Diakonieverbandes GmbH
[Not yet recruiting]
Hemer, Germany, 58675
Contact:Contact: Monika Serke, MD
Lungenfachklinik Immenhausen
[Recruiting]
Immenhausen, Germany, 34376
Contact:Contact: Achim Rittmeyer, MD
Klinikum der Universität zu Köln, Klinik I für Innere Medizin
[Not yet recruiting]
Köln, Germany, 50937
Contact:Contact: Jürgen Wolf, MD
Klinikum der Johannes Gutenberg Universität, III. Med. Klinik und Poliklinik
[Not yet recruiting]
Mainz, Germany, 55131
Contact:Contact: Jürgen Alt, MD
Pius Hospital, Klinik für Hämatologie und Onkologie
[Recruiting]
Oldenburg, Germany, 26121
Contact:Contact: Frank Griesinger, MD
Rems-Murr-Klinikum Winnenden, Klinik für Hämatologie, Onkologie und Palliativmedizin
[Not yet recruiting]
Winnenden, Germany, 71364
Contact:Contact: Maria Netchaeva
Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken
[Not yet recruiting]
Würzburg, Germany, 97078
Contact:Contact: Pius Jung, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:
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